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1. Olavarria E, Parker S, Craddock C, Philpott N, Tiniakou M, Chase A, Kanfer E, Apperley JF, Goldman JM: Collection of Ph-negative progenitor cells from interferon responsive patients with chronic myeloid leukemia: effect of granulocyte-colony-stimulating factor mobilization. Haematologica; 2000 Jun;85(6):647-52
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  • [Title] Collection of Ph-negative progenitor cells from interferon responsive patients with chronic myeloid leukemia: effect of granulocyte-colony-stimulating factor mobilization.
  • BACKGROUND AND OBJECTIVE: The observation that patients with chronic myeloid leukemia (CML) may relapse following stem cell transplantation because of Philadelphia positive cells contaminating the graft have led to a variety of strategies to reduce this contamination.
  • This study investigate the feasibility of collective, Ph-re cells from patients with CML in chronic phase.
  • DESIGN AND METHODS: A total of 18 patients with chronic myeloid leukemia in chronic phase who had responded to varying degrees to treatment with interferon-a (IFN) were subjected to mobilization with granulocyte colony-stimulating factors and peripheral blood progenitor cell collection.
  • Nine patients were in complete cytogenetic remission (CCR) and nine were partial responders.
  • IFN was stopped 2 to 4 weeks before the procedure.
  • RESULTS: Five patients underwent one collection procedure only, 10 underwent two procedures and 3 patients had three collections.
  • The median number of nucleated cells (NC) per patient collected was 10.2 x 10(8)/kg (4.4-19.7) and the median number of CD34(+) cells was 2.5 x 10(6)/kg (0.4-9.4).
  • The median percentage of Ph- negative metaphases for patients in CCR was 100% (73-100).
  • Patients not in CCR had a higher level of Ph-positive cells in their collections (median 23%, range 0-79%, p=0.01).
  • Of the nine patients in CCR, 8 had at least one apheresis from which progenitor cells were 100% Ph-negative; conversely, patients not in CCR had detectable Ph-positive cells in every collection.
  • Four patients have undergone autologous stem cell transplantation.
  • INTERPRETATION AND CONCLUSIONS: It was possible to collect sufficient Ph negative progenitor cells from patients in CCR but collections from other patients contained significant numbers of Ph-positive cells.
  • [MeSH-major] Interferons / pharmacology. Leukapheresis / methods. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / pathology. Philadelphia Chromosome. Stem Cells / cytology
  • [MeSH-minor] Adult. Antigens, CD34 / blood. Cell Count. Cytogenetics. Disease-Free Survival. Female. Graft Survival. Granulocyte Colony-Stimulating Factor / pharmacology. Hematopoietic Stem Cell Mobilization. Humans. Male. Middle Aged. Transplantation, Autologous. Transplantation, Homologous


2. Bashir Q, De Lima MJ, McMannis JD, Garcia-Manero G, Shpall E, Kantarjian H, Cortes JE, O'Brien SM, Jones D, Qazilbash M, Wei W, Giralt SA, Champlin RE, Hosing C: Hematopoietic progenitor cell collection in patients with chronic myelogenous leukemia in complete cytogenetic remission after imatinib mesylate therapy. Leuk Lymphoma; 2010 Aug;51(8):1478-84
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  • [Title] Hematopoietic progenitor cell collection in patients with chronic myelogenous leukemia in complete cytogenetic remission after imatinib mesylate therapy.
  • The introduction of BCR-ABL tyrosine kinase inhibitors such as imatinib has changed the treatment of chronic myelogenous leukemia (CML).
  • More than 75% of patients achieve complete cytogenetic remission (CCR) after treatment with imatinib, which provides an opportunity to collect minimally involved hematopoietic progenitor stem cell (HPC) products.
  • In order to assess the feasibility of HPC collection in patients with CML, we prospectively enrolled 24 patients who achieved CCR on therapy with imatinib.
  • A CD34+ cell yield of > or =2.0 x 10(6)/kg body weight was obtained in 16/22 (73%) patients.
  • Patients who stopped imatinib for at least 3 weeks prior to HPC collection had significantly higher CD34+ cell yields (median: 6.52 x 10(6)/kg body weight) when compared with patients who continued imatinib through the collection (median: 3.74 x 10(6)/kg body weight).
  • Mobilization with granulocyte colony-stimulating factor (G-CSF) did not increase the levels of BCR-ABL transcript.
  • With a mean follow-up of 46 months, all patients but one were in CCR.
  • In conclusion, a significant number of CD34+ cells can be safely collected in patients with CML who are on imatinib therapy, but CD34+ cell yields improve when imatinib is temporarily withheld.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Hematopoietic Stem Cell Mobilization. Hematopoietic Stem Cells / physiology. Leukapheresis / methods. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adult. Antigens, CD34 / metabolism. Benzamides. Feasibility Studies. Female. Fusion Proteins, bcr-abl / genetics. Humans. Imatinib Mesylate. Male. Middle Aged. Prospective Studies. Protein-Tyrosine Kinases / genetics. RNA, Messenger / genetics. Remission Induction. Reverse Transcriptase Polymerase Chain Reaction. Survival Rate. Treatment Outcome

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  • (PMID = 20658954.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P30 CA016672
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD34; 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 0 / RNA, Messenger; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.2 / Fusion Proteins, bcr-abl
  • [Other-IDs] NLM/ NIHMS629570; NLM/ PMC4188823
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3. Ghalaut VS, Pahwa MB, Sunita, Ghalaut PS: Alteration in lipid profile in patients of chronic myeloid leukemia before and after chemotherapy. Clin Chim Acta; 2006 Apr;366(1-2):239-42
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  • [Title] Alteration in lipid profile in patients of chronic myeloid leukemia before and after chemotherapy.
  • BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of pleuripotent hematopoietic progenitor cells characterized by excessive proliferation and accumulation of granulocytes and occasionally red blood cells and platelets.
  • METHODS: We examined 30 newly diagnosed and proved cases of CML admitted in medical wards or attending a clinical hematology clinic.
  • In addition to routine hematological investigations, lipid profile was done in all the patients at the time of presentation, 4-6 weeks after the start of chemotherapy and 6 months after the chemotherapy even if some of the patients were not in remission.
  • RESULTS: Total serum cholesterol, HDL-cholesterol and LDL-cholesterol concentrations increased significantly after chemotherapy whereas serum triglyceride and VLDL-C cholesterol concentrations did not increase significantly.
  • Also, lipid concentrations were correlated with disease activity.
  • We found from the present study that low lipid concentrations are associated with poor prognosis of the disease.
  • CONCLUSION: We suggest that the estimation of lipid profile may be helpful in evaluating the response to chemotherapy in CML patients.
  • [MeSH-major] Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood. Lipids / blood
  • [MeSH-minor] Adolescent. Adult. Aged. Cholesterol / blood. Cholesterol, HDL / blood. Cholesterol, LDL / blood. Cholesterol, VLDL / blood. Female. Humans. Male. Middle Aged. Remission Induction. Time Factors. Treatment Outcome. Triglycerides / blood

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  • (PMID = 16386722.001).
  • [ISSN] 0009-8981
  • [Journal-full-title] Clinica chimica acta; international journal of clinical chemistry
  • [ISO-abbreviation] Clin. Chim. Acta
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Cholesterol, HDL; 0 / Cholesterol, LDL; 0 / Cholesterol, VLDL; 0 / Lipids; 0 / Triglycerides; 97C5T2UQ7J / Cholesterol
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4. Fang B, Li N, Song Y, Han Q, Zhao RC: Standard-dose imatinib plus low-dose homoharringtonine and granulocyte colony-stimulating factor is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis who have failed prior single-agent therapy with imatinib. Ann Hematol; 2010 Nov;89(11):1099-105
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  • [Title] Standard-dose imatinib plus low-dose homoharringtonine and granulocyte colony-stimulating factor is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis who have failed prior single-agent therapy with imatinib.
  • We investigated the efficacy of the induction therapy involving granulocyte colony-stimulating factor (G-CSF) and low-dose homoharringtonine as well as standard-dose imatinib, which we called the G-CSF + homoharringtonine + imatinib (GHI) regimen, in patients with chronic myelogenous leukemia (CML) in blast crisis who have failed prior single-agent therapy with imatinib.
  • The GHI regimen consisted in a unique induction course where imatinib was administered at 400 mg day(-1) until remission, together with homoharringtonine (1 mg/m(2) s.c. twice daily for 14 days every 28 days), and G-CSF, which was administered 1 day before chemotherapy (5 µg/kg s.c. daily).
  • Patients who responded to induction treatment and who had a matched donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT).
  • The results demonstrates that the GHI regimen re-induce hematologic responses or improve the cytogenetic responses in all evaluable patients.
  • Furthermore, eligible patients have benefited from allo-HSCT after response to this induction treatment.
  • We conclude that the GHI regimen may overcome disease-poor response to conventional doses of imatinib and this approach deserves further evaluation as frontline therapy for newly diagnosed CML.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Blast Crisis / drug therapy. Granulocyte Colony-Stimulating Factor / therapeutic use. Harringtonines / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adolescent. Adult. Benzamides. Drug Therapy, Combination. Female. Humans. Imatinib Mesylate. Male. Middle Aged. Treatment Failure. Treatment Outcome. Young Adult

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  • (PMID = 20499235.001).
  • [ISSN] 1432-0584
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Harringtonines; 0 / Piperazines; 0 / Pyrimidines; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 6FG8041S5B / homoharringtonine; 8A1O1M485B / Imatinib Mesylate
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5. Huang X, Guo N, Ren H, Zhang Y, Gao Z, Lu D: An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation. Chin Med J (Engl); 2003 May;116(5):736-41
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  • [Title] An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation.
  • OBJECTIVE: To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.
  • METHODS: Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n = 11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n = 9).
  • After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively.
  • One achieved partial remission and died of interstitial pneumonia; and the other one showed no response.
  • Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion.
  • Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon.
  • And the other one with AML showed no response to the therapy.
  • CONCLUSION: Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse.
  • Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.
  • [MeSH-major] Granulocyte Colony-Stimulating Factor / therapeutic use. Hematopoietic Stem Cell Mobilization. Hematopoietic Stem Cell Transplantation. Leukemia / therapy

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  • (PMID = 12875692.001).
  • [ISSN] 0366-6999
  • [Journal-full-title] Chinese medical journal
  • [ISO-abbreviation] Chin. Med. J.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 143011-72-7 / Granulocyte Colony-Stimulating Factor
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6. 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.
  • BACKGROUND: Interferon-alpha (IFN) is known to promote graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo BMT).
  • 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.
  • Subsequently, IFN was given to patients without significant GVHD or rapidly progressive disease.
  • The outcome after DLI with regard to remission rate, disease-free survival and GVHD was analysed.
  • 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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7. Robak T: Purine nucleoside analogues in the treatment of myleoid leukemias. Leuk Lymphoma; 2003 Mar;44(3):391-409
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  • [Title] Purine nucleoside analogues in the treatment of myleoid leukemias.
  • However, several investigations have revealed that these agents are active also in acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML).
  • Synergistic interaction between FA or 2-CdA with cytarabine (Ara-C) have been demonstrated in both preclinical and clinical studies.
  • PNA enhance the cell concentration of Ara-CTP, which is active metabolite of Ara-C.
  • It is likely that the addition of granulocyte colony stimulating factor (G-CSF) may further improve the effects of FA (FLAG) or 2-CdA (CLAG).
  • The addition of anthracyclines to induction therapy does not appear to result in a substantial advantage in terms of CR achievement and duration.
  • An alternative approach to increase FLAG activity might be the addition of investigational drugs with novel mechanism of action, such as topoiromerase I inhibitors.
  • The addition of anthracyclines to induction therapy does not appear to result in a substantial advantage in terms of CR achievement and duration.
  • Clinical studies have confirmed the efficacy of PNA alone or in combination protocols in the treatment of AML.
  • However, early relapses remain a significant problem in a majority of refractory or relapsed patients in CR after treatment with PNA based regimens.
  • To prolong remission duration or even cure AML, auto--or allo stem cell transplantation should be considered.
  • However, FAMP or 2-CdA containing regimens may impair mobilization and collection of stem cells from peripheral blood for autotransplantation.
  • Few studies have analyzed the role of PNA in CML.
  • 2-CdA, FAMP and DCF can induce hematologic response in chronic phase of CML but cytogenetic responses have not been observed.
  • Preliminary results suggest, that PNA used alone or in combination may be used as palliation in blast phase of the disease.
  • However, currently, the role of these agents in CML is insignificant because of the high activity of Glivec in this disease.
  • Finally, PNA, especially FA play an important role in non-myeloablative conditioning regimens for allogenic stem cell transplantation in high-risk patients, possibly also with myeloid malignancies.
  • [MeSH-major] Antimetabolites, Antineoplastic / therapeutic use. Cladribine / therapeutic use. Leukemia, Myeloid / drug therapy. Pentostatin / therapeutic use. Vidarabine / analogs & derivatives. Vidarabine / therapeutic use
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Antibiotics, Antineoplastic / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child. Child, Preschool. Clinical Trials as Topic. Cytarabine / administration & dosage. Drug Synergism. Female. Granulocyte Colony-Stimulating Factor / administration & dosage. Hematopoietic Stem Cell Mobilization. Humans. Infant. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Male. Middle Aged. Peripheral Blood Stem Cell Transplantation. Remission Induction. Salvage Therapy. Transplantation Conditioning. Transplantation, Autologous. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 12688309.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Antimetabolites, Antineoplastic; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 395575MZO7 / Pentostatin; 47M74X9YT5 / Cladribine; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; FLAG protocol
  • [Number-of-references] 128
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8. Martinelli G, Montefusco V, Amabile M, Lemoli RM, Terragna C, Testoni N, Ottaviani E, Rosti G, de Vivo A, Rizzi S, Russo D, Bregoli M, Tura S: Quantitative evaluation of BCR-ABL amount of transcript post mobilization with G-CSF of peripheral blood stem cells from chronic myeloid leukemia patients in cytogenetic response. Leuk Lymphoma; 2000 Sep;39(1-2):113-20
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  • [Title] Quantitative evaluation of BCR-ABL amount of transcript post mobilization with G-CSF of peripheral blood stem cells from chronic myeloid leukemia patients in cytogenetic response.
  • We studied nine patients affected by chronic myeloid leukemia (CML Ph+ and bcr-abl positive) and treated with alpha-interferon (alpha-INF) in order to: first, to evaluate the feasibility of a mobilization of peripheral blood stem cells induced by granulocyte-colony-stimulating factor (G-CSF) and the contamination by Ph+ cells and second, to quantify the amount of bcr-abl leukemia associated transcript by a quantitative assay during mobilization procedures, and post mobilization follow-up.
  • Eight achieved a complete karyotypic remission before mobilization obtained with discontinuation of alpha-INF for few days and G-CSF at a dosage of 15 microg/kg/day for 5-7 consecutive days.
  • By quantitative-competitive polymerase chain reaction (QC-PCR) assay, all the leukaphereses and bone marrow samples during post mobilization follow up were studied to determine the amount of bcr-abl transcript.
  • Karyotypic and molecular analysis on evaluable leukapheresis showed that all the harvests were Ph negative and bcr-abl positive: in seven cases the levels of bcr-abl transcript were higher or equal to the pre-apheresis status.
  • In three out of four patients, who underwent more than one leukapheresis procedure, we noticed a decreasing amount of bcr-abl contamination from the first to the last apheresis.
  • Our results suggest that in patients who achieved a complete or major cytogenetic conversion with alpha-INF, it is possible to obtain a sufficient amount of PBSC for autografting by leukapheresis following priming G-CSF therapy and that the amount of neoplastic transcript does not seem to increase.
  • [MeSH-major] Fusion Proteins, bcr-abl / genetics. Granulocyte Colony-Stimulating Factor / pharmacology. Hematopoietic Stem Cell Mobilization. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • [MeSH-minor] Adolescent. Adult. Blood Component Removal. Cytogenetic Analysis. Female. Follow-Up Studies. Humans. Male. Middle Aged. Philadelphia Chromosome. RNA, Neoplasm / blood

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  • (PMID = 10975389.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] SWITZERLAND
  • [Chemical-registry-number] 0 / RNA, Neoplasm; 143011-72-7 / Granulocyte Colony-Stimulating Factor; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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9. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Schaefer HE: [Histologic and hematological findings in CML. A comparative immunohistochemical-morphometric and clinical study on bone marrow biopsies from 604 patients derived from two institutes of pathology (Cologne/Freiburg)]. Pathologe; 2000 Jan;21(1):39-54
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  • [Title] [Histologic and hematological findings in CML. A comparative immunohistochemical-morphometric and clinical study on bone marrow biopsies from 604 patients derived from two institutes of pathology (Cologne/Freiburg)].
  • [Transliterated title] Histologische und hämatologische Befunde bei der CML. Eine immunhistochemisch-morphometrische und klinische Vergleichsstudie an Beckenkammbiopsien von 604 Patienten aus zwei Instituten für Pathologie (Köln/Freiburg).
  • An immunohistochemical and morphometric study was performed on bone marrow biopsies in 604 patients with chronic myelogenous leukemia (CML) to compare morphological and clinical features and to evaluate effects of interferon (IFN) and chemotherapy.
  • This finding is in line with the close functional relationship between megakaryopoiesis and fibroblasts regarding the complex pathomechanism of myelofibrosis.
  • The latter was observed in about 28% of patients already at diagnosis.
  • In a similar way, the frequency of CD68(+) macrophages was correlated with the amount of Ret40f(+) nucleated erythroid precursors, implicating an involvement of this cell lineage in iron turnover, hemoglobin synthesis, and degradation of the expelled nuclei from normoblasts.
  • The (alpha-D-galactosyl residue-expressing) Pseudo-Gaucher cells were detectable in 30% of pretreatment specimens.
  • Moreover, significant associations were calculable between reduction in erythropoiesis or increase in fibers with clinical features such as hemoglobin level, percentages of myelo- and erythroblasts in the peripheral blood, and spleen size.
  • These variables are in keeping with more advanced stages of CML.
  • Based on our morphometric evaluations, a classification into three different histological subgroups: granulocytic, megakaryocytic, and myelofibrotic was carried out.
  • The dynamics of myelofibrosis and changes of major cell lineages during treatment were readily demonstrable by calculating corresponding indices.
  • These included the ratios between quantitative differences of corresponding variables at repeated examinations and time.
  • Thus, in patients with complete hematological remission following IFN administration, regeneration of erythropoiesis was found to be accompanied by an increase in the total number of CD68(+) macrophages, including activated subpopulations.
  • Histological subgroups showed a transition from a (nonfibrotic) granulocytic and megakaryocyte pattern to the myelofibrotic subtype in about 40% of patients.
  • This change was opposed to a numerical reduction in the myelofibrotic subtype which occurred in 17 patients (36%), but predominantly in those under HU therapy.
  • In conclusion, the striking heterogeneity of bone marrow features in CML warrants a careful morphological evaluation of trephine biopsies and appropriate means of processing to achieve relevant correlations with clinical data and, thus, allows a more elaborate insight into the dynamics of the disease process.
  • [MeSH-major] Bone Marrow / pathology. Hematopoietic Stem Cells / pathology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • [MeSH-minor] Biopsy. Blood Cell Count. Bone Marrow Cells / cytology. Erythropoiesis. Humans. Immunohistochemistry. Macrophages / pathology. Reference Values. Retrospective Studies

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  • (PMID = 10663668.001).
  • [ISSN] 0172-8113
  • [Journal-full-title] Der Pathologe
  • [ISO-abbreviation] Pathologe
  • [Language] ger
  • [Publication-type] Comparative Study; English Abstract; Journal Article
  • [Publication-country] GERMANY
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10. Brummendorf TH, Ersoz I, Hartmann U, Balabanov S, Wolke H, Paschka P, Lahaye T, Berner B, Bartolovic K, Kreil S, Berger U, Gschaidmeier H, Bokemeyer C, Hehlmann R, Dietz K, Lansdorp PM, Kanz L, Hochhaus A: Normalization of previously shortened telomere length under treatment with imatinib argues against a preexisting telomere length deficit in normal hematopoietic stem cells from patients with chronic myeloid leukemia. Ann N Y Acad Sci; 2003 May;996:26-38
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Normalization of previously shortened telomere length under treatment with imatinib argues against a preexisting telomere length deficit in normal hematopoietic stem cells from patients with chronic myeloid leukemia.
  • In somatic cells, telomere repeats are lost with each cell division, eventually leading to genetic instability and cellular senescence.
  • In previous studies, we described substantial and disease stage-specific telomere shortening in peripheral blood (PB) leukocytes from patients with chronic myeloid leukemia (CML).
  • Here, we sought to determine whether age-adjusted telomere length in PB granulocytes (deltaTEL(gran)) is associated with response to treatment with the selective tyrosine kinase inhibitor imatinib.
  • A total of 517 samples from 206 patients in chronic phase (CP), accelerated phase (AP), and blast crisis (BC) before and up to 706 days after initiation of imatinib therapy (median: 144 days) were analyzed by quantitative fluorescence in situ hybridization of interphase cells in suspension (Flow-FISH); telomere fluorescence was expressed in molecular equivalents of soluble fluorochrome units (MESF).
  • Telomere length in samples from start of treatment up to day 144 was significantly shorter (mean +/- SE; -1.5 +/- 0.3 kMESF) compared to samples from patients treated for more than 144 days (-0.8 +/- 0.3 kMESF, p = 0.035).
  • In patients with repeated measurements, a significant increase in telomere length under treatment was observed.
  • Median telomere length in major remission was found to be significantly longer compared to patients without response to treatment measured either by cytogenetics (n = 246, p < 0.05), interphase FISH (n = 204, p = 0.002), or quantitative RT-PCR (n = 371, p < 0.05).
  • In conclusion, the increase in telomere length under treatment with imatinib reflects a shift from Ph+ to Ph- cells in the PB of patients with CML.
  • [MeSH-major] Hematopoietic Stem Cells / cytology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. Piperazines / pharmacology. Pyrimidines / pharmacology. Telomere / drug effects. Telomere / pathology
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Aging. Benzamides. Female. Granulocytes / pathology. Humans. Imatinib Mesylate. In Situ Hybridization, Fluorescence. Interphase. Male. Middle Aged. Telomerase / metabolism






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