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1. Porter DL, Alyea EP, Antin JH, DeLima M, Estey E, Falkenburg JH, Hardy N, Kroeger N, Leis J, Levine J, Maloney DG, Peggs K, Rowe JM, Wayne AS, Giralt S, Bishop MR, van Besien K: NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant; 2010 Nov;16(11):1467-503
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation.
  • Relapse is a major cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT).
  • Treatment options for relapse have been inadequate, and the majority of patients ultimately die of their disease.
  • There is no standard approach to treating relapse after alloHSCT.
  • Withdrawal of immune suppression and donor lymphocyte infusions are commonly used for all diseases; although these interventions are remarkably effective for relapsed chronic myelogenous leukemia, they have limited efficacy in other hematologic malignancies.
  • Conventional and novel chemotherapy, monoclonal antibody therapy, targeted therapies, and second transplants have been utilized in a variety of relapsed diseases, but reports on these therapies are generally anecdotal and retrospective.
  • As such, there is an immediate need for well-designed, disease-specific trials for treatment of relapse after alloHSCT.
  • This report summarizes current treatment options under investigation for relapse after alloHSCT in a disease-specific manner.
  • In addition, recommendations are provided for specific areas of research necessary in the treatment of relapse after alloHSCT.
  • [MeSH-major] Hematologic Neoplasms / therapy. Hematopoietic Stem Cell Transplantation. Neoplasm Recurrence, Local / therapy
  • [MeSH-minor] Hodgkin Disease / therapy. Humans. Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Leukemia, Myeloid, Acute / therapy. Lymphocyte Transfusion. Lymphoma, Non-Hodgkin. Multiple Myeloma / therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Recurrence. Transplantation, Homologous. Treatment Failure

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  • (PMID = 20699125.001).
  • [ISSN] 1523-6536
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / K24 CA117879
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Other-IDs] NLM/ NIHMS241037; NLM/ PMC2955517
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2. Wassmann B, Klein SA, Scheuring U, Pfeifer H, Martin H, Gschaidmeier H, Hoelzer D, Ottmann OG: Hematologic and cytogenetic remission by STI571 (Glivec) in a patient relapsing with accelerated phase CML after second allogeneic stem cell transplantation. Bone Marrow Transplant; 2001 Oct;28(7):721-4
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  • [Title] Hematologic and cytogenetic remission by STI571 (Glivec) in a patient relapsing with accelerated phase CML after second allogeneic stem cell transplantation.
  • We describe the clinical activity of the ABL kinase inhibitor STI571 in a patient with accelerated phase of chronic myeloid leukemia (CML) relapsing after a second allogeneic BMT and with minimal levels of donor chimerism.
  • STI571 induced sustained hematological and cytogenetic remission combined with controllable GvHD, therapeutic goals not achieved by two preceding allogeneic transplants and repeated donor lymphocyte transfusions (DLT).
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Bone Marrow Transplantation. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Accelerated Phase / drug therapy. Neoplasm Recurrence, Local / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Salvage Therapy
  • [MeSH-minor] Antineoplastic Agents, Alkylating / therapeutic use. Benzamides. Colitis / chemically induced. Combined Modality Therapy. Enzyme Inhibitors / adverse effects. Enzyme Inhibitors / therapeutic use. Female. Graft Survival. Graft vs Host Disease / etiology. Graft vs Leukemia Effect. Humans. Hydroxyurea / therapeutic use. Imatinib Mesylate. Immunosuppression. Interferon-alpha / therapeutic use. Leukemia, Myeloid, Chronic-Phase / drug therapy. Leukemia, Myeloid, Chronic-Phase / therapy. Lymphocyte Transfusion. Middle Aged. Neoplasm, Residual. Neutropenia / chemically induced. Remission Induction. Transplantation Conditioning. Transplantation, Homologous

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  • (PMID = 11704799.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antineoplastic Agents, Alkylating; 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / Interferon-alpha; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; X6Q56QN5QC / Hydroxyurea
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3. Pawson R, Potter MN, Theocharous P, Lawler M, Garg M, Yin JA, Rezvani K, Craddock C, Rassam S, Prentice HG: Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant. Br J Haematol; 2001 Dec;115(3):622-9
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  • [Title] Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant.
  • Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics.
  • Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control.
  • We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor.
  • Transplants were well tolerated with no treatment-related deaths.
  • The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this.
  • FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Bone Marrow Transplantation. Cytarabine / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Idarubicin / administration & dosage. Leukemia / therapy. Transplantation Conditioning / methods. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives
  • [MeSH-minor] Acute Disease. Adult. Anemia, Refractory, with Excess of Blasts / therapy. Child. Child, Preschool. Disease-Free Survival. Female. Filgrastim. Graft vs Host Disease / immunology. Graft vs Host Disease / prevention & control. Humans. Leukemia, Myeloid / therapy. Male. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Recombinant Proteins. Recurrence. Reoperation. Retrospective Studies. Survival Rate. Transplantation, Homologous

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  • (PMID = 11736947.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Recombinant Proteins; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; PVI5M0M1GW / Filgrastim; ZRP63D75JW / Idarubicin; Ida-FLAG protocol
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4. Platzbecker U, Thiede C, Freiberg-Richter J, Helwig A, Mohr B, Prange G, Füssel M, Köhler T, Ehninger G, Bornhäuser M: Treatment of relapsing leukemia after allogeneic blood stem cell transplantation by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF. Ann Hematol; 2001 Mar;80(3):144-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Treatment of relapsing leukemia after allogeneic blood stem cell transplantation by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF.
  • Ten patients with high-risk acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) relapsing early (< 1 year, n = 8) or late (> or = 1 year, n = 2) after allogeneic transplantation were treated with cytoreductive chemotherapy followed by unmanipulated peripheral blood stem cell transplantation (PBSCT) from related (n = 3) and unrelated donors (n = 7).
  • In order to enhance the graft-versus-leukemia effect, patients received no graft-versus-host disease (GVHD) prophylaxis and granulocyte-macrophage colony-stimulating factor (GM-CSF) was given at a dose of 60 micrograms/m2 after transplant.
  • Eight out of ten patients achieved complete remission: one out of two patients with AML and late relapse is in good condition with limited chronic GVHD more than 1 year after the second PBSCT.
  • One patient with blastic phase CML achieved molecular remission but died +330 days after the second PBSCT because of intracranial bleeding.
  • Of the remaining five patients, three died of infectious complications on days +36, +70, and +27, one patient died with extramedullary relapse on day +35, and one from multi-organ failure in association with acute GVHD on day +32 after the second PBSCT.
  • Although several patients achieved complete remission, the high risk of GVHD and treatment-related mortality should be kept in mind, especially when a second transplant is considered during a period of less than 12 months after the first procedure.
  • Monitoring of minimal residual disease might predict relapse thus preventing high doses of cytotoxic drugs for reconditioning.
  • The potential of GM-CSF to enhance the graft-versus-leukemia reactivity after cytoreductive therapy for allogeneic transplantation warrants further investigation.
  • [MeSH-major] Graft vs Leukemia Effect. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid / therapy. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Female. Graft vs Host Disease. Granulocyte-Macrophage Colony-Stimulating Factor. Humans. Karyotyping. Male. Middle Aged. Recurrence. Transplantation Conditioning. Transplantation, Homologous


5. Au WY, Lie AK, Ma SK, Wan TS, Liang R, Chan EC, Kwong YL: Tyrosine kinase inhibitor STI571 in the treatment of Philadelphia chromosome-positive leukaemia failing myeloablative stem cell transplantation. Bone Marrow Transplant; 2002 Oct;30(7):453-7
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  • [Title] Tyrosine kinase inhibitor STI571 in the treatment of Philadelphia chromosome-positive leukaemia failing myeloablative stem cell transplantation.
  • Eight patients with Philadelphia chromosome-positive (Ph(+)) leukaemia relapsing from stem cell transplantation (SCT) (one syngeneic and seven allogeneic) were treated with the tyrosine kinase inhibitor STI571.
  • Five patients relapsing as chronic myeloid leukaemia (CML) in chronic phase achieved a complete haematological response, with complete and major cytogenetic responses occurring in four and one cases, respectively.
  • One patient became negative for BCR/ABL in the bone marrow.
  • Three patients relapsed as acute leukaemia (two CML in myeloblastic crisis and one Ph(+) acute lymphoblastic leukaemia), all of whom achieved haematological and cytogenetic responses.
  • One patient also became BCR/ABL negative.
  • However, pancytopenia and graft-versus-host disease led to cessation of treatment in the remaining two cases, which was followed by disease recurrence refractory to further STI treatment.
  • Our results showed that Ph(+) leukaemic relapses after SCT might respond well to STI571 therapy.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / administration & dosage. Pyrimidines / administration & dosage. Salvage Therapy / methods
  • [MeSH-minor] Adolescent. Adult. Benzamides. Drug Evaluation. Female. Fusion Proteins, bcr-abl / genetics. Humans. Imatinib Mesylate. Male. Middle Aged. Myeloablative Agonists. RNA, Neoplasm / analysis. Recurrence. Remission Induction. Transplantation Conditioning / methods. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 12368958.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Benzamides; 0 / Myeloablative Agonists; 0 / Piperazines; 0 / Pyrimidines; 0 / RNA, Neoplasm; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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6. Min CK, Eom KS, Lee S, Kim DW, Lee JW, Min WS, Kim CC: Effect of induced GVHD in leukemia patients relapsing after allogeneic bone marrow transplantation: single-center experience of 33 adult patients. Bone Marrow Transplant; 2001 May;27(9):999-1005
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  • [Title] Effect of induced GVHD in leukemia patients relapsing after allogeneic bone marrow transplantation: single-center experience of 33 adult patients.
  • In a retrospective single center study, we examined the outcome of induced GVHD in leukemia patients relapsing after allogeneic BMT.
  • Thirty-three adult patients with leukemia (15 AML, 3 ALL, and 15 CML) persisting or relapsing 1-36 months (median, 6) after allogeneic BMT underwent various immune manipulations and consequently developed acute and/or chronic GVHD at our center.
  • Immunotherapies to elicit GVHD comprised chemotherapy followed by PBSC (n = 18), non-myeloablative transplant (n = 2), PBL followed by IFN-alpha (n = 5), PBL alone (n = 3), abrupt cessation of CsA (n = 3), and CsA withdrawal combined with IFN-alpha (n = 2).
  • Twenty-four (72.7%) patients obtained a remission including complete hematological or cytogenetic remission, respectively, for acute leukemias or CML.
  • Twelve (63.2%) of 19 dead patients died due to treatment-related toxicities; five patients from acute GVHD, three from GVHD followed by infections and four from infections.
  • By multivariate Cox analysis, only chronic GVHD resulted in a higher probability of disease-free survival (P = 0.026).
  • Eight patients who had both acute GVHD < or = grade I and chronic GVHD are all alive without leukemia.
  • We conclude that acute GVHD is associated with considerable toxicity while chronic GVHD plays a role in retaining remission in leukemia relapsing after allogeneic BMT.
  • [MeSH-major] Bone Marrow Transplantation / adverse effects. Graft vs Host Disease / etiology. Leukemia / therapy
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Agents / administration & dosage. Antineoplastic Agents / toxicity. Cyclosporine / administration & dosage. Cyclosporine / toxicity. Female. Graft vs Leukemia Effect. Hematopoietic Stem Cell Transplantation / adverse effects. Hematopoietic Stem Cell Transplantation / methods. Hematopoietic Stem Cell Transplantation / mortality. Humans. Immunotherapy / adverse effects. Interferon-alpha / administration & dosage. Interferon-alpha / toxicity. Leukocyte Transfusion / adverse effects. Male. Recurrence. Remission Induction. Retrospective Studies. Survival Rate. Transplantation, Homologous / adverse effects. Transplantation, Homologous / mortality


7. de Lima M, van Besien K, Gajewski J, Khouri I, Andersson B, Korbling M, Champlin R, Giralt S: High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant. Bone Marrow Transplant; 2000 Aug;26(3):333-8
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  • [Title] High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant.
  • Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a poor prognosis.
  • We studied the use of melphalan 180 mg/m2 followed by allogeneic peripheral blood stem cells (PBSC) as salvage treatment for patients relapsing after related (n = 7) or matched unrelated transplants (n = 3).
  • Diagnoses were AML (n = 4), ALL (n = 3), biphenotypic acute leukemia (n = 2) and CML in blast crisis (n = 1).
  • Eight patients were beyond first relapse and none were in remission.
  • The median time from previous transplant to relapse was 146 days (range 66-206).
  • The median time to an absolute neutrophil count >0.5 x 10(9)/l and to a platelet count >20 x 10(9)/l was 11 and 13 days, respectively.
  • Acute GVHD grades II-III occurred in two subjects, and chronic GVHD in four.
  • Seven patients achieved CR, but relapsed at a median of 116 days (range 56-614).
  • Leukemia was the cause of death in eight patients.
  • This treatment produced responses in the majority of this poor prognosis group.
  • However, durable remissions were not observed, and new treatments to consolidate the responses achieved in this setting are needed.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Bone Marrow Transplantation. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy. Melphalan / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • [MeSH-minor] Acute Disease. Adult. Child. Chronic Disease. Combined Modality Therapy. Dose-Response Relationship, Drug. Female. Graft vs Host Disease / etiology. Humans. Male. Middle Aged. Pilot Projects. Remission Induction. Transplantation Chimera


8. Wu HX, Qian SX, Hong M, Zhang YP, Lu H, Zhang R, Zhang XY, Chen LJ, Lu RN, Zhang SJ, Liu P, Ge Z, Fan L, Wang L, Xu J, Tian T, Zhu Y, Qiu HX, Xu W, Sheng RL, Li JY: [Allogeneic peripheral blood stem cell transplantation for 75 cases of hematologic malignancies]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2008 Dec;16(6):1330-3
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  • 75 patients included 35 patients with chronic myeloid leukemia (CML), 30 patients with acute myeloid leukemia, 5 patients with severe aplastic anemia, 3 patients with acute lymphocytic leukemia, one patients with multiple myeloma and one patients with paroxysmal nocturnal hemoglobinuria.
  • Relapsing patients after transplantation received DLI and/or chemotherapy.
  • Patient with CML were treated with imatinib.
  • The median time for the initial hematopoietic reconstitution was 15 (5-25) days.
  • Among 29 dead patients, 9 died of disease relapse, 7 died of III-IV grade of acute GVHD and 7 died of severe infection (2 patients developed interstitial pneumonia).
  • 9 out of 14 patients received haploidentical transplantation were alive, and the time of event-free survival was 30 (6-53) months, the mean survival time of 5 died patients was 7 (2-17) months.
  • It is concluded that allo-PBSCT is effective to treat refractory hematologic diseases, and DLI/or chemotherapy should be used in the patients relapsing after transplantation.

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  • (PMID = 19099638.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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9. Elmaagacli AH: Real-time PCR for monitoring minimal residual disease and chimerism in patients after allogeneic transplantation. Int J Hematol; 2002 Aug;76 Suppl 2:204-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Real-time PCR for monitoring minimal residual disease and chimerism in patients after allogeneic transplantation.
  • Real-time PCR is a new fluorometric method for cycle-to-cycle quantification of PCR product growth rates.
  • The real-time PCR method is fast and associated with a high reproducibility rate.
  • There are real-time PCR methods for patients with CML, AML and ALL patients with inv(16), t(8;21), t(15;17); t(1;19) and other chromosomal aberrations.
  • For patients with AML monitoring MRD is useful to identify patients who were at high risk for relapse after receiving chemotherapy.
  • In patients with CML monitoring MRD might be helpful to assess success of after allogeneic SCT, or response to therapies with interferon alfa or STI 571.
  • We found, that it is possible to estimate the relapse stage in CML after SCT by the amount of bcr-abl fusion transcript detected using a real-time PCR method.
  • The median measured bcr-abl amount differ significantly (P<0.001) between the various stages, which has relevant clinical implications because it enables early therapeutic decisions in relapsing patients after transplant as e.g. the application of DLI to induce graft-versus-leukemia effects.
  • Using real-time PCR it is possible to detect differences at alleles between recipient and donor at a single nucleotide basis (SNP) for chimerism analysis.
  • The real-time PCR method enables to achieve a high a sensitivity of up to 1x10(-4), which is much more sensitive than all other chimerism methods including VNTR-PCR, STR-PCR.
  • Furthermore, chimerism in male recipients with a female donor can be monitored also by detecting y-chromosome specific sequences by real-time PCR after transplant, which might be the most sensitive method to detect host type gene sequences.
  • All in all, new real-time PCR methods offer a fast, reliable and very sensitive method to evaluate MRD and chimerism in patients after allogeneic SCT and therefore, to help to identify patients who are at high risk for leukemic relapse.
  • [MeSH-major] Neoplasm, Residual / diagnosis. Polymerase Chain Reaction / standards
  • [MeSH-minor] Hematopoietic Stem Cell Transplantation. Humans. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Transplantation Chimera. Transplantation, Homologous

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  • [Cites] Br J Haematol. 2002 Jan;116(1):87-93 [11841400.001]
  • [Cites] Blood. 2002 Jan 15;99(2):443-9 [11781223.001]
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  • [Cites] J Mol Diagn. 2001 Nov;3(4):141-9 [11687597.001]
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  • [Cites] Eur J Haematol. 2001 Nov-Dec;67(5-6):302-8 [11872078.001]
  • (PMID = 12430926.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Japan
  • [Number-of-references] 7
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10. Kim YJ, Kim DW, Lee S, Chung NG, Hwang JY, Kim YL, Min CK, Kim CC: Preemptive treatment of minimal residual disease post transplant in CML using real-time quantitative RT-PCR: a prospective, randomized trial. Bone Marrow Transplant; 2004 Mar;33(5):535-42
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  • [Title] Preemptive treatment of minimal residual disease post transplant in CML using real-time quantitative RT-PCR: a prospective, randomized trial.
  • Immunotherapy in the form of donor lymphocyte infusions in early-phase relapse might be advantageous as it induces a higher response, but this may be offset by increased toxicity, especially during the early period after transplantation.
  • Among 45 consecutive patients receiving an allograft for CML, 13 patients were diagnosed to have molecular relapse (MRel), as defined by real-time quantitative reverse transcriptase-polymerase chain reaction, and another four patients were diagnosed to have cytogenetic relapse (CRel) within 6 months.
  • Patients with MRel were randomly assigned to either a 'no therapy' group (group A, n=6), in which immunotherapy was reserved until CRel, or an 'immunotherapy' group (group B, n=7).
  • In patients relapsing directly into CRel (n=4), immunotherapy induced MR in two patients (50%).
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Neoplasm, Residual / diagnosis. Neoplasm, Residual / therapy. Reverse Transcriptase Polymerase Chain Reaction
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Benzamides. Combined Modality Therapy. Disease Progression. Female. Graft vs Host Disease / drug therapy. Humans. Imatinib Mesylate. Immunosuppressive Agents / administration & dosage. Male. Middle Aged. Piperazines / administration & dosage. Polymerase Chain Reaction. Prospective Studies. Pyrimidines / administration & dosage. Recurrence. Remission Induction. Survival Analysis. Transplantation, Homologous

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  • (PMID = 14716340.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Benzamides; 0 / Immunosuppressive Agents; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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11. Kim YJ, Kim DW, Lee S, Kim YL, Hwang JY, Park YH, Kim HJ, Lee JW, Min WS, Kim CC: Cytogenetic clonal evolution alone in CML relapse post-transplantation does not adversely affect response to imatinib mesylate treatment. Bone Marrow Transplant; 2004 Jan;33(2):237-42
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  • [Title] Cytogenetic clonal evolution alone in CML relapse post-transplantation does not adversely affect response to imatinib mesylate treatment.
  • Good prognosis after imatinib mesylate treatment has been reported if cytogenetic clonal evolution (CE) is the only criterion of accelerated phase (AP) chronic myelogenous leukemia (CML).
  • To evaluate the impact of CE upon imatinib treatment in post-transplant settings, responses and toxicities in the relapsed AP-CE were analyzed in comparison with those in the relapsed chronic phase (CP).
  • Nonhematological adverse events were mild and tolerable in both groups and only one (7%) of the 13 patients experienced recurrent graft-versus-host disease after imatinib treatment.
  • Although this is a relatively small group of patients, we suggest that imatinib mesylate should be considered as a front-line treatment for relapsed CML as it showed the high response rate and low toxicity.
  • We also suggest that CE alone is not an important factor in the induction of cytogenetic and molecular remissions in post-transplant relapse.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Hematopoietic Stem Cell Transplantation. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / administration & dosage. Pyrimidines / administration & dosage
  • [MeSH-minor] Adult. Benzamides. Clone Cells. Combined Modality Therapy. Female. Graft vs Host Disease / drug therapy. Humans. Imatinib Mesylate. Male. Middle Aged. Neoplasm, Residual / drug therapy. Neoplasm, Residual / pathology. Recurrence. Remission Induction

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  • (PMID = 14628081.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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12. Larghero J, Leguay T, Mourah S, Madelaine-Chambrin I, Taksin AL, Raffoux E, Bastie JN, Degos L, Berthaud P, Marolleau JP, Calvo F, Chomienne C, Mahon FX, Rousselot P: Relationship between elevated levels of the alpha 1 acid glycoprotein in chronic myelogenous leukemia in blast crisis and pharmacological resistance to imatinib (Gleevec) in vitro and in vivo. Biochem Pharmacol; 2003 Nov 15;66(10):1907-13
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  • [Title] Relationship between elevated levels of the alpha 1 acid glycoprotein in chronic myelogenous leukemia in blast crisis and pharmacological resistance to imatinib (Gleevec) in vitro and in vivo.
  • The Abl tyrosine kinase inhibitor imatinb is becoming a standard for the treatment of chronic myelogenous leukemia (CML).
  • However, Bcr-Abl gene mutations have been reported mainly in relapsing or resistant patients.
  • We aimed to investigate if alpha 1 acid glycoprotein (AGP), an acute phase drug binding protein, could be a biological marker for pharmacological resistance to imatinib in nine patients in acute phase CML.
  • No mutation in the adenosine triphosphate domain of Abl were detected before the initiation of imatinib therapy.
  • By using in vitro tests combining various imatinib concentrations (1-10 microM) with purified human AGP (1 and 3 mg/mL), we demonstrate that imatinib-induced apoptosis of K562 or fresh leukemic CML cells is abrogated or reduced.
  • In patients with CML in blastic phase, AGP levels could reflect pharmacological resistance to imatinib, suggesting that increased dosage of imatinib or the use of a competitor to drug binding should be recommended to optimize the therapeutic effect of the drug.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Blast Crisis / pathology. Drug Resistance, Neoplasm / physiology. Orosomucoid / metabolism. Piperazines / pharmacology. Pyrimidines / pharmacology
  • [MeSH-minor] Apoptosis. Benzamides. Humans. Imatinib Mesylate. K562 Cells. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. Tumor Cells, Cultured

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  • (PMID = 14599548.001).
  • [ISSN] 0006-2952
  • [Journal-full-title] Biochemical pharmacology
  • [ISO-abbreviation] Biochem. Pharmacol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Orosomucoid; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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13. Porter DL, Levine BL, Bunin N, Stadtmauer EA, Luger SM, Goldstein S, Loren A, Phillips J, Nasta S, Perl A, Schuster S, Tsai D, Sohal A, Veloso E, Emerson S, June CH: A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood; 2006 Feb 15;107(4):1325-31
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  • Donor lymphocyte infusions (DLIs) induce potent graft versus tumor (GVT) effects for relapsed chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (SCT) but are disappointing for other diseases.
  • We performed a phase 1 trial of ex vivo-activated DLI (aDLI) for 18 patients with relapse after SCT.
  • Patients with aggressive malignancies received induction chemotherapy, and all patients received conventional DLI (median, 1.5 x 10(8) mononuclear cells/kg) followed 12 days later by aDLI.
  • Seven patients developed acute graft versus host disease (GVHD) (5 grade I-II, 2 grade III), and 4 developed chronic GVHD.
  • Eight patients achieved complete remission, including 4 of 7 with acute lymphocytic leukemia (ALL), 2 of 4 with acute myelogenous leukemia (AML), 1 with chronic lymphocytic leukemia (CLL), and 1 of 2 with non-Hodgkin lymphoma (NHL).
  • Four complete responders relapsed while 4 remain alive in remission a median 23 months after aDLI.
  • [MeSH-major] Antigens, CD28 / blood. Antigens, CD8 / blood. Leukemia / therapy. Lymphocyte Transfusion / adverse effects. Lymphoma / therapy. Stem Cell Transplantation / adverse effects

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  • (PMID = 16269610.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD; 0 / Antigens, CD28; 0 / Antigens, CD8
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14. Blair A, Goulden NJ, Libri NA, Oakhill A, Pamphilon DH: Immunotherapeutic strategies in acute lymphoblastic leukaemia relapsing after stem cell transplantation. Blood Rev; 2005 Nov;19(6):289-300
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  • [Title] Immunotherapeutic strategies in acute lymphoblastic leukaemia relapsing after stem cell transplantation.
  • Acute lymphoblastic leukaemia (ALL) responds well to chemotherapy and the majority of children and a significant proportion of adults are cured of their disease after primary therapy.
  • However, a number of patients relapse and allogeneic transplantation following conditioning with chemotherapy and radiotherapy offers the possibility of long-term survival in a proportion of these patients.
  • A significant number of patients with ALL develop disease that is refractory to further therapy.
  • The infusion of unmodified donor lymphocytes (DLI) following relapse after allogeneic transplantation has been shown to be curative in patients with chronic myeloid leukaemia (CML).
  • In vivo studies to date suggest that educated T-cells may have a role to play in the treatment of relapsed and refractory ALL in the future.
  • [MeSH-major] Immunotherapy, Adoptive. Lymphocyte Transfusion. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Stem Cell Transplantation. Transplantation Conditioning
  • [MeSH-minor] Adult. Child. Child, Preschool. Dendritic Cells / immunology. Dendritic Cells / transplantation. Female. Graft vs Leukemia Effect / immunology. Humans. Male. Neoplasm Proteins / immunology. Secondary Prevention. T-Lymphocyte Subsets / immunology. T-Lymphocyte Subsets / transplantation. T-Lymphocytes, Cytotoxic / immunology. T-Lymphocytes, Cytotoxic / transplantation. Transplantation, Homologous

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  • (PMID = 16275419.001).
  • [ISSN] 0268-960X
  • [Journal-full-title] Blood reviews
  • [ISO-abbreviation] Blood Rev.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Scotland
  • [Chemical-registry-number] 0 / Neoplasm Proteins
  • [Number-of-references] 89
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15. Usuki K, Kanda Y, Iijima K, Iki S, Hirai H, Urabe A: [Chronic myelogenous leukemia in cessation of therapy after sustained CCR with interferon]. Rinsho Ketsueki; 2003 Dec;44(12):1161-5
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  • [Title] [Chronic myelogenous leukemia in cessation of therapy after sustained CCR with interferon].
  • In Ph(+) CML patients who achieved complete cytogenetic response (CCR) with interferon-alpha (IFN) treatment, how long the treatment should be continued has not well been investigated.
  • We report here 2 CML cases who stopped the treatment after CCR had been sustained with IFN for 2-3 years.
  • A 49-year-old male (case 1) achieved CCR 6 months after the initiation of IFN treatment.
  • CCR had been maintained for 3 years, and then the treatment was ceased.
  • CCR has been sustained without any therapy for 4 years.
  • In case 2, a 50-year-old male, CCR was achieved after 8 years of IFN treatment, and maintained for 2 years.
  • One month after cessation of the treatment, CML relapsed cytogenetically.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Interferon-alpha / administration & dosage. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • [MeSH-minor] Cytogenetic Analysis. Drug Administration Schedule. Humans. Male. Middle Aged. Neoplasm Recurrence, Local. Remission Induction. Reverse Transcriptase Polymerase Chain Reaction. Time Factors. Treatment Outcome

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  • (PMID = 14978932.001).
  • [ISSN] 0485-1439
  • [Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology
  • [ISO-abbreviation] Rinsho Ketsueki
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha
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16. Grigg A, Kannan K, Schwarer AP, Spencer A, Szer J: Chemotherapy and granulocyte colony stimulating factor-mobilized blood cell infusion followed by interferon-alpha for relapsed malignancy after allogeneic bone marrow transplantation. Intern Med J; 2001 Jan-Feb;31(1):15-22
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  • [Title] Chemotherapy and granulocyte colony stimulating factor-mobilized blood cell infusion followed by interferon-alpha for relapsed malignancy after allogeneic bone marrow transplantation.
  • This property may also be used to enhance a graft-versus-leukaemia effect (GVL) after donor leucocyte infusion (DLI), a mode of therapy increasingly offered to patients relapsing after allo BMT.
  • AIM: The aims of the present study were to examine the efficacy and toxicity of IFN therapy administered after granulocyte colony-stimulating factor (G-CSF)-stimulated blood cells given as DLI in patients with acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL), acute undifferentiated leukaemia (AUL) and multiple myeloma relapsing after allo BMT.
  • METHODS: Between October 1996 and September 1999, 27 patients (16 AML, four ALL, three CML, three multiple myeloma, one AUL) who relapsed after allo BMT were treated with chemotherapy followed by DLI, collected after G-CSF stimulation in all but two cases.
  • RESULTS: Eighteen patients received IFN following DLI, 14 of whom developed significant GVHD (grade II-IV acute or extensive chronic); thereafter, GVHD resolved with cessation of IFN alone in four patients, but 10 required systemic immunosuppression.
  • Twenty-three patients were given chemotherapy and DLI as initial treatment of relapse; 10 achieved complete remission (CR), in four patients this was only after the onset of GVHD.
  • The other four patients received chemotherapy and DLI as a consolidation of a chemotherapy-induced remission.
  • The CR was durable only in patients with CML (3 of 3) and AML (4 of 8).
  • CONCLUSIONS: Treatment with IFN induced GVHD in the majority of patients receiving DLI.
  • The induction of GVHD and GVL by this approach produced excellent results in patients with CML and modest results in AML, but appeared to be less effective in myeloma and ALL.
  • [MeSH-major] Bone Marrow Transplantation. Granulocyte Colony-Stimulating Factor / therapeutic use. Interferon-alpha / therapeutic use. Leukocyte Transfusion
  • [MeSH-minor] Acute Disease. Adult. Female. Graft vs Host Disease / etiology. Graft vs Leukemia Effect / drug effects. Humans. Leukemia / drug therapy. Leukemia / therapy. Leukemia, Myeloid / drug therapy. Leukemia, Myeloid / therapy. Male. Middle Aged. Multiple Myeloma / etiology. Remission Induction. Survival Analysis. Treatment Outcome

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  • (PMID = 11478351.001).
  • [ISSN] 1444-0903
  • [Journal-full-title] Internal medicine journal
  • [ISO-abbreviation] Intern Med J
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Interferon-alpha; 143011-72-7 / Granulocyte Colony-Stimulating Factor
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17. Kobbe G, Schneider P, Rohr U, Fenk R, Neumann F, Aivado M, Dietze L, Kronenwett R, Hünerlitürkoglu A, Haas R: Treatment of severe steroid refractory acute graft-versus-host disease with infliximab, a chimeric human/mouse antiTNFalpha antibody. Bone Marrow Transplant; 2001 Jul;28(1):47-9
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  • [Title] Treatment of severe steroid refractory acute graft-versus-host disease with infliximab, a chimeric human/mouse antiTNFalpha antibody.
  • Patients with severe aGVHD not responding to treatment with steroids have a poor prognosis.
  • Patients (CML 2, MM 1, AML 1) developed grade III-IV GVHD at a median of 34 days (range 15-76) after myeloablative PBSCT (two), donor lymphocyte infusion for relapsed CML (one) or non-myeloablative PBSCT (one), respectively.
  • All patients had severe intestinal involvement in addition to skin and/or liver disease and had received treatment with high-dose steroids (four) for a median of 11 days (range 5-17) in addition to CsA (four) and MMF (three).
  • At present two patients are alive >200 days after therapy, one with limited cGVHD.
  • Infliximab is apparently an active drug for the treatment of aGVHD.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Graft vs Host Disease / drug therapy
  • [MeSH-minor] Acute Disease. Adult. Animals. Anti-Inflammatory Agents / administration & dosage. Female. Hematologic Neoplasms / complications. Hematologic Neoplasms / therapy. Hematopoietic Stem Cell Transplantation / adverse effects. Humans. Infliximab. Male. Mice. Middle Aged. Recombinant Fusion Proteins / administration & dosage. Salvage Therapy. Steroids / therapeutic use. Transplantation, Homologous / adverse effects. Treatment Outcome. Tumor Necrosis Factor-alpha / immunology

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  • (PMID = 11498743.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents; 0 / Antibodies, Monoclonal; 0 / Recombinant Fusion Proteins; 0 / Steroids; 0 / Tumor Necrosis Factor-alpha; B72HH48FLU / Infliximab
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18. Blau IW, Basara N, Bischoff M, Günzelmann S, Römer E, Kirsten D, Schmetzer B, Kiehl MG, Fauser AA: Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant. Bone Marrow Transplant; 2000 Jan;25(1):41-5
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  • [Title] Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant.
  • We report 27 patients with relapsed acute or chronic leukemia who underwent a second hematopoietic stem cell transplant (HSCT) from a related or unrelated donor.
  • Seventeen patients were diagnosed with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL) and four with chronic myeloid leukemia (CML).
  • Relapse was diagnosed between 1 and 45 months after the first HSCT.
  • Sixteen patients who relapsed had received an autologous transplant initially and 11 an allogeneic transplant.
  • Ten patients relapsed within 6 months and 17 patients later than 6 months.
  • Chemotherapy was used as reinduction for relapse after HSCT in 16 patients who had received an autologous transplant and in three who had received an allogeneic transplant, since the latter did not respond to reduction of immunosuppression to induce a graft-versus-leukemia (GVL) reaction.
  • Five of these 19 patients (26%) achieved complete remission (CR), seven patients did not respond to chemotherapy and seven achieved a partial remission (PR).
  • One patient is alive and disease-free after two allogeneic transplants (day +1538), eight patients, who relapsed after an autologous transplant followed by an allogeneic transplant (days +248 to +1140), acute myeloid leukaemia (n = 6) and chronic myeloid leukemia (n = 2) are alive and disease-free.
  • It is suggested that a second HSCT is possible for patients with leukemia relapse following the first autologous transplant.
  • A second transplant might also be offered to patients relapsing after the first allogeneic HSCT.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia / pathology. Leukemia / therapy
  • [MeSH-minor] Acute Disease. Adult. Chronic Disease. Female. Humans. Male. Middle Aged. Recurrence. Survival Analysis. Transplantation, Homologous

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  • (PMID = 10654013.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] ENGLAND
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