melphalan has been researched along with Leukemia--Myelogenous--Chronic--BCR-ABL-Positive* in 20 studies
4 trial(s) available for melphalan and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive
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Impact of tailored patient education on adherence of patients with chronic myeloid leukaemia to tyrosine kinase inhibitors: a randomized multicentre intervention study.
The aim of this study was to evaluate the influence of tailored patient education on adherence to tyrosine kinase inhibitor medication among patients with chronic myeloid leukaemia.. Management of chronic myeloid leukaemia has changed dramatically during the last decade. While medication adherence is crucial to clinical response, little is known about how to improve patients' adherence.. Randomized multicentre intervention study.. The study was conducted between June 2012-August 2014. Eighty-six patients with chronic myeloid leukaemia who had been on tyrosine kinase inhibitor medication for at least six months from eight hospitals were randomized into intervention and control groups. Intervention combined nurse-conducted medication counselling, an information booklet, video and website and text message reminders. Patients were interviewed to assess medication adherence using Morisky's 8-Item Medication Adherence Scale at baseline and nine months.. Medication adherence improved with the adherence aids used. At nine months, 51% of patients were highly adherent in the intervention group, compared with 21% in the control group. Adherence improved for a higher proportion of patients in the intervention group than the control group (49% vs. 18%). Morisky's score decreased in almost half of control group cases. Patients were most satisfied with face-to-face counselling (86%) and the information booklet (83%) and least satisfied with text messages (9%).. Tailored patient education improved the medication adherence of patients with chronic myeloid leukaemia. Without this, adherence behaviour tended to decline. Personal communication with a nurse proved to be an essential part of adherence support and should not be ignored. Topics: Adult; Aged, 80 and over; Female; Humans; Immunoglobulin G; Internet; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Medication Adherence; Melphalan; Middle Aged; Patient Education as Topic; Protein-Tyrosine Kinases; Reminder Systems; Text Messaging | 2016 |
Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-alpha.
In chronic myelogenous leukemia (CML), autologous stem cell transplantation could be a promising new approach for patients with no cytogenetic response after interferon alpha (IFN-alpha) therapy. We report data on 28 CML patients autotransplanted in chronic phase with peripheral blood progenitor cells mobilized with G-CSF (5 microg/kg/day x 5 days) given subcutaneously while continuing IFN-alpha therapy. At mobilization, 23 patients (82%) were in complete hematological remission (CHR), 16 (57%) achieved a minor cytogenetic response (mcr). We obtained, after stimulation, a median of 37.4 x 10(9)/l (6.9-108) white blood cells, 7.2 x 10(8)/kg (2.2-16.6) mononuclear cells, 39 x 10(4)/kg (4.8-403.5) CFU-GM and 4.2 x 10(6)/kg (0-58.6) CD34+ cells. Six patients received GM-CSF after transplantation. All patients engrafted, with no significant influence stemming from the Sokal index score and pretransplantation IFN-alpha therapy duration. The first cytogenetic evaluation after transplantation showed 11 (39%) major cytogenetic response (Mcr), and nine (32%) mcr with no significant correlation between these responses, the Sokal index score, and pretransplantation IFN-alpha therapy duration, although there was a significant impact from GM-CSF administration (P=0.01). After transplantation, 26 patients received IFN-alpha alone or associated with hydroxyurea. The median follow-up was 12 months after transplantation and 57 months after diagnosis. At the time of follow-up, nine patients were in CHR, six remained stable in chronic phase, three presented an mcr and one remained in Mcr. At the last follow-up, 22 patients were alive. We conclude that the results of this strategy are encouraging in poor IFN-alpha responders but that other prospective studies that try to maintain the cytogenetic responses obtained immediately after transplantation are needed. Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Interferon-alpha; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Middle Aged; Neutrophils; Transplantation Conditioning | 2000 |
Successful treatment of accelerated and blastic phase of chronic myeloid leukemia with high-dose interferon alpha and hydroxyurea: a novel approach.
Six patients with either acceleration or blast crisis of transformed chronic myeloid leukemia (CML) were treated with high-dose interferon alpha in combination with hydroxyurea. All patients responded to the treatment by reversal to stable chronic phase. Two of these patients responded repeatedly during their course of disease. Median time for return to chronic phase was 4 weeks. Adverse side-effects such as nausea, vomiting, hairloss, fever, prolonged cytopenia were not observed. Topics: Acetaminophen; Adult; Aged; Analgesics, Non-Narcotic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Bone Marrow Transplantation; Busulfan; Combined Modality Therapy; Cytarabine; Humans; Hydroxyurea; Interferon-alpha; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Middle Aged | 1995 |
Autologous peripheral stem cell transplantation of the blastic phase of chronic myeloid leukemia following sequential high-dose cytosine arabinoside and melphalan.
Blast-phase chronic myelogenous leukemia (CML) is the terminal phase in CML and is uniformly fatal. We treated 12 patients with blast-phase CML with a program of high-dose cytarabine 3.0 g/m2 and melphalan 140 mg/m2, followed by reinfusion of stem cells obtained from peripheral blood during the chronic phase. Seven patients achieved either a partial or complete hematologic remission, while five patients showed no response to therapy. One patient returned to chronic phase features with loss of a chromosomal abnormality acquired at blast phase, restoration of hematopoiesis, and a decrease in the amount of bone marrow blasts to less than 10%. Six patients cleared their peripheral blasts and showed recovery of their myeloid and platelet lineages, but all six required treatment for acceleration within 3 months. Of the five nonresponding patients, three died with aplastic bone marrow, one patient never cleared peripheral blasts after chemotherapy, and one patient had evidence of peripheral blasts 3 weeks after the autologous stem cell reinfusion. None of the patients returned to a normal karyotype. The ablative regimen was effective in eradicating bone marrow blasts to < 10% in 8 of 10 patients in whom interpretable bone marrow samples were performed following chemotherapy. Overall, the median survival for all patients from the time of stem cell reinfusion was 5.5 months. We conclude that autotransplants with peripheral blood can successfully be used to support hematopoiesis during high-dose therapy for CML blast crisis, however, has no role by itself in the curative therapy of blast crisis CML. A small number of patients can be restored to chronic phase features, and this may provide an opportunity to administer subsequent alternative treatments designed to eradicate the malignant stem cell population. Autotransplants with stem cells may also be used as therapy for patients without a histocompatible marrow donor. However, the autotransplant may be more effective when used during the chronic phase of CML, with the use of hematopoietic growth factors, and with reinfusion of stem cells depleted of the malignant Philadelphia chromosome-positive clone. Topics: Adult; Blood Transfusion, Autologous; Combined Modality Therapy; Cytarabine; Dose-Response Relationship, Drug; Female; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Middle Aged; Transplantation, Autologous | 1994 |
16 other study(ies) available for melphalan and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive
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Chronic myeloid leukemia following treatment for bilateral retinoblastoma.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Combined Modality Therapy; Cryotherapy; Dasatinib; Eye Enucleation; Humans; Infant; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Light Coagulation; Male; Melphalan; Neoplasms, Multiple Primary; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Radiotherapy, Adjuvant; Remission Induction; Retinoblastoma | 2018 |
Myeloid sarcoma as the initial presentation of chronic myelogenous leukemia, medullary chronic phase in era of tyrosine kinase inhibitors: A report of 11 cases.
Topics: Adult; Aged; Antineoplastic Agents; Boronic Acids; Bortezomib; Female; Humans; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Prognosis; Protein Kinase Inhibitors; Pyrazines; Sarcoma, Myeloid; Survival Analysis | 2015 |
Imatinib increases cytotoxicity of melphalan and their combination allows an efficient killing of chronic myeloid leukemia cells.
BCR/ABL positive cells are known to be resistant to DNA damage induced by chemotherapy while they are sensitive to imatinib (IM), a tyrosine kinase inhibitor (TKI). To evaluate whether this drug can increase the activity of cytotoxic drugs on BCR/ABL positive cells, we measured the toxicity of cytosine arabinoside (ARA-C), hydroxyurea (HU) and melphalan (MEL), after a pretreatment of 24 h with IM on K562 cell line. The highest cytotoxic effect was seen when the TKI was followed by MEL; our results indicate that inhibition of BCR/ABL activity by IM increased the cytotoxicity of MEL by favoring the DNA damage induced by this drug and by shortening the time for DNA repair at the G2/M checkpoint. A stronger activation of some genes involved in both intrinsic and extrinsic apoptotic pathways was also observed with IM/MEL combination compared to IM or MEL alone. The drugs association was further tested in a type of BaF3 cells (TonB.210) where the BCR-ABL expression is inducible by doxycycline; in this model it was confirmed that a reduction of BCR/ABL activity resulted in an increased susceptibility to the cytotoxic effect of MEL. Furthermore, we studied the effect of IM/MEL treatment on the proliferative potential of myeloid progenitors of six CML patients at diagnosis. The analysis of CFU-GM and BFU-E colonies demonstrated that the IM/MEL combination was more effective than IM alone in reducing the overall number of colonies and the number of copies of BCR/ABL. In conclusion, our work shows that inhibition of BCR/ABL activity increases the toxicity of MEL and allows an efficient killing of leukemic cells, suggesting that a clinical development of this approach could have therapeutic advantages for CML patients. Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzamides; Cell Cycle; Cytarabine; DNA Damage; Drug Synergism; Gene Expression; Genes, abl; Humans; Hydroxyurea; Imatinib Mesylate; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Melphalan; Piperazines; Pyrimidines; Tumor Stem Cell Assay | 2011 |
Glucosylceramide synthase inhibitor PDMP sensitizes chronic myeloid leukemia T315I mutant to Bcr-Abl inhibitor and cooperatively induces glycogen synthase kinase-3-regulated apoptosis.
Inactivation of glycogen synthase kinase (GSK)-3 has been implicated in cancer progression. Previously, we showed an abundance of inactive GSK-3 in the human chronic myeloid leukemia (CML) cell line. CML is a hematopoietic malignancy caused by an oncogenic Bcr-Abl tyrosine kinase. In Bcr-Abl signaling, the role of GSK-3 is not well defined. Here, we report that enforced expression of constitutively active GSK-3 reduced proliferation and increased Bcr-Abl inhibition-induced apoptosis by nearly 1-fold. Bcr-Abl inhibition activated GSK-3 and GSK-3-dependent apoptosis. Inactivation of GSK-3 by Bcr-Abl activity is, therefore, confirmed. To reactivate GSK-3, we used glucosylceramide synthase (GCS) inhibitor PDMP to accumulate endogenous ceramide, a tumor-suppressor sphingolipid and a potent GSK-3 activator. We found that either PDMP or silence of GCS increased Bcr-Abl inhibition-induced GSK-3 activation and apoptosis. Furthermore, PDMP sensitized the most clinical problematic drug-resistant CML T315I mutant to Bcr-Abl inhibitor GNF-2-, imatinib-, or nilotinib-induced apoptosis by >5-fold. Combining PDMP and GNF-2 eliminated transplanted-CML-T315I-mutants in vivo and dose dependently sensitized primary cells from CML T315I patients to GNF-2-induced proliferation inhibition and apoptosis. The synergistic efficacy was Bcr-Abl restricted and correlated to increased intracellular ceramide levels and acted through GSK-3-mediated apoptosis. This study suggests a feasible novel anti-CML strategy by accumulating endogenous ceramide to reactivate GSK-3 and abrogate drug resistance. Topics: 1-Deoxynojirimycin; Animals; Apoptosis; Cell Line, Tumor; Ceramides; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Enzyme Inhibitors; Female; Genes, abl; Glucosyltransferases; Glycogen Synthase Kinase 3; Humans; Immunoglobulin G; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Melphalan; Mice; Mice, SCID; Morpholines; Mutation; Neoplasms, Experimental; Pyrimidines; Transplantation, Heterologous | 2011 |
Whither the bone marrow transplant?
Bone marrow transplantation (BMT) has become an accepted and important medical intervention which has become a routine part of medical practice. Its utility has, however, been questioned recently in a number of diseases in which its role has been clearly established on the basis that there are better non-transplant therapeutic options. The suspicion that these moves to eradicate BMT as an option may not stem from purely scientific reasons has prompted the preparation of these personal reflections. I will focus this discussion only on two diseases in which BMT has been shown to be useful: chronic myelogenous leukemia (CML) and multiple myeloma (MM). Topics: Antineoplastic Agents; Benzamides; Bone Marrow Transplantation; Developed Countries; Developing Countries; Drug Costs; Drug Utilization; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Melphalan; Mexico; Multiple Myeloma; Piperazines; Protein Kinase Inhibitors; Pyrimidines; Spain; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; United States | 2010 |
[The standard treatments for patients with hematological malignancies in Japan].
Recently, the standard treatments for hematological malignancies have shown dramatic improvement. For chronic myeloid leukemia, imatinib has become the treatment of choice in initial treatment, and its long-term effectiveness and safety have been confirmed. For acute myelogenous leukemia, cytarabine with anthracycline agent is believed to be the standard treatment in first remission induction therapy. To improve the efficacy of the first remission induction chemotherapy, the addition of gemutuzumab ozogamicin has been investigated intensively all over the world. However, there are many obstacles to conducting its clinical trial in Japan. The addition of rituximab to CHOP improves the survival of patients with diffuse large B-cell lymphoma. For follicular lymphoma patients, rituximab with conventional chemotherapies are considered the standard treatments, but the question of which conventional chemotherapy is better is unsolved. MP therapy had long been the standard treatment for elderly patients with multiple myeloma, but MP therapy plus thalidomide with MP therapy has been found to be superior. In patients who are candidates for autologous stem-cell transplantation, VAD therapy or high-dose dexamethasone therapy followed by autologous stem-cell transplantation is considered the treatment of choice. But the number of transplantations and the timing of second transplantation need more investigation. Considering the overall situation with regard to the standard treatments of hematological malignancies in Japan, there is little difference in practice from western countries. However, the framework of conducting clinical trials to investigate standard treatment in Japan is unsatisfactory. Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Melphalan; Multiple Myeloma; Prednisone; Rituximab; Survival Rate; Vincristine | 2007 |
Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia.
Allogeneic hematopoietic stem-cell transplantation (HSCT) remains an effective strategy for inducing durable remission in chronic myeloid leukemia (CML). Reduced-intensity conditioning (RIC) regimens extend HSCT to older patients and those with comorbidities who would otherwise not be suitable candidates for HSCT. The long-term efficacy of this approach is not established. We evaluated outcomes of 64 CML patients with advanced-phase disease (80% beyond first chronic phase), not eligible for myeloablative preparative regimens due to older age or comorbid conditions, who were treated with fludarabine-based RIC regimens. Donor type was matched related (n =30), 1 antigen-mismatched related (n =4), or matched unrelated (n =30). With median follow-up of 7 years, overall survival (OS) and progression-free survival (PFS) were 33% and 20%, respectively, at 5 years. Incidence of treatment-related mortality (TRM) was 33%, 39%, and 48% at 100 days, and 2 and 5 years after HSCT, respectively. In multivariate analysis, only disease stage at time of HSCT was significantly predictive for both OS and PFS. RIC HSCT provides adequate disease control in chronic-phase CML patients, but alternative treatment strategies need to be explored in patients with advanced disease. TRM rates are acceptable in this high-risk population but increase over time. Topics: Adolescent; Adult; Aged; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Middle Aged; Myeloablative Agonists; Recurrence; Retrospective Studies; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine | 2007 |
[Comparison of the long term results between two conditioning regimens MCC and BuCy in chronic myelocytic leukemia after allogeneic stem cell transplantation].
To observe and evaluate the long term survival of patients with chronic myelocytic leukemia transplanted with MCC and BuCy conditioning regimens.. Fourteen cases were treated with MCC regimen (Melphanlan 170 mg/m2 x d x 1, MeCCNU 400 mg/m2 x d x 1, CTX 60 mg/kg x d x 2) and the median follow up time was 6 years; 16 cases were treated with BuCy regimen (Busulfan 4 mg/kg x d x 4, CTX 60 mg/kg x d x 2) and the median follow up time was 4 year.. All the patients were engrafted successfully. 4 of 10 patients examined in MCC group showed mixed chimerism at day 100 after transplantation, whereas only 1 of 12 patients examined in BuCy group showed mixed chimerism. All the patients became complete donor source later without any DLI. The 5-year disease-free survival rate was 71.4% for MCC group and 62.5% for BuCy group. The transplant related mortality and relapse rate were 21% and 7% for MCC group, whereas those were 25% and 12% for BuCy group, respectively. The regimen related toxicity was relatively lower in MCC group and the median duration of hospitalization was 39 days (25-55 days) for patients with MCC regimen, and 55 days (39-90 days) for BuCy regimen.. MCC regimen has a partial ablative effect on CML and the long term disease-free survival is the same as that of BuCy regimen. In regard to the cost-effect efficacy, MCC regimen has a substantial advantage over BuCy regimen. Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cyclophosphamide; Drug Administration Schedule; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Middle Aged; Semustine; Stem Cell Transplantation; Treatment Outcome | 2006 |
Autotransplantation for chronic myeloid leukemia: is it useful?
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Bone Marrow Purging; Busulfan; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Imatinib Mesylate; Interferons; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Melphalan; Multicenter Studies as Topic; Piperazines; Pyrimidines; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous | 2002 |
A new preconditioning regimen with melphalan, busulphan and total body irradiation followed by low-dose immunosuppressant in allogeneic haemopoietic stem cell transplantation.
Twenty adult patients with high-risk leukaemia underwent allogeneic haemopoietic stem cell transplantation after melphalan, busulphan and total body irradiation followed by short-term methotrexate and low-dose cyclosporine or tacrolimus. Three patients developed veno-occlusive disease and no patient developed renal dysfunction. Seven patients experienced grade II-IV acute graft-versus-host disease (aGVHD) and five patients experienced grade III-IV. The 3-year probabilities of relapse and leukaemia-free survival were 22 +/- 11% (95% confidence interval) and 50 +/- 11%, respectively. These data suggest that this preconditioning regimen followed by a low-dose immunosuppressant provided a more anti-leukaemic effect without increased regimen-related toxicity and aGVHD. Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cyclosporine; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Melphalan; Middle Aged; Tacrolimus; Whole-Body Irradiation | 1999 |
Collection of peripheral blood stem cells after a preceding autograft: unfavorable effect of prior interferon-alpha therapy.
Eighty-eight previously autografted (78 transplanted twice and 10 once) myeloma patients who had no cryopreserved stem cells available for possible future use received G-CSF for mobilization of stem cells. One-fourth of the patients had progressive disease at the time of apheresis. All patients had received 200 mg/m2 melphalan for the first transplant. The interval between the preceding transplant and the harvest was 5-68 months (median 29). A total of 0.46-9.16 (median 3.03) x 10(6) CD34+ cells/kg were collected. More than 2 x 10(6)/kg CD34+ cells were collected in 76% of the patients, and > or = 5 x 10(6)/kg in 14%. On multivariate analysis, patients with platelet counts of > or = 200 x 10(9)/l (P < 0.0001), those who had not received any myelosuppressive chemotherapy between the last transplant and the collection (P = 0.02), and those who had received interferon-alpha for < or = 6 months (P = 0.03) had better collections. Eleven of 12 patients autografted with these cells had prompt neutrophil recovery (median 10 days to 0.5 x 10(9)/l) but recovery to 50 x 10(9)/l platelets was delayed or incomplete in 11 of 12. We conclude that it is possible to harvest peripheral blood stem cells with G-CSF stimulation in patients who have been autografted previously. Limited data suggest that platelet recovery may be suboptimal when these cells are used. These findings have practical implications for patients with malignant diseases in remission after autografting who may be candidates for future salvage therapy but have no stem cells stored, and for patients with chronic myeloid leukemia who are on long-term interferon-alpha therapy to attain cytogenetic remission for eventual collection of normal stem cells. Topics: Adult; Aged; Antigens, CD34; Antineoplastic Agents, Alkylating; Blood Cells; Dose-Response Relationship, Drug; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Interferon-alpha; Leukapheresis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Melphalan; Middle Aged; Multiple Myeloma; Stem Cells; Transplantation, Autologous | 1999 |
[MMC conditioning regimen (Melphalan, MeCCNU and cyclophosphamide) followed by allogeneic peripheral blood stem cells transplantation for chronic myeloid leukemia].
This paper reports 3 cases of allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) for the patients with chronic myeloid leukemia (CML). The patients received MMC preparative regimen with high dose chemotherapy (Melphalan 170 mg/m2, p.o. on Day-5, MeCCNU 400 mg/m2, p.o. on Day-4, and Cyclophosphomide 60 mg/kg/day, i.v. on Days-3 and -2). The HLA-identical sibling donors received filgrastim (rhG-CSF) for mobilization at a dose of 300 micrograms/day for 6 days. Leukaphereses were done at the 6th day of mobilization. A median of 8000 ml (2 times total blood volume) of blood was processed the collecting: 2.5-4.5 x 10(8)/kg MNC, 12.8-20.0 x 10(6)/kg CD34+ cells (including 4.8-7.5 x 10(6)/kg CD34+CD33-, 8.0-13.0 x 10(6)/kg CD34+CD33+), and 3.5-4.3 x 10(5)/kg CFU-GM. Cyclosporin A and methotrexate were used for GVHD prophylaxis. Hematopoitic function recovered as for 14-20 days to > 0.5 x 10(9)/L of neutrophil count, and for 16-34 days to > 20 x 10(9)/L of platelet count. At day + 100, chromosome analysis of bone marrow cells showed that complete chimera without ph1 positive chromosome in Cases 1 and 3, and a partial chimera with 73% donor karyotype in Case 2. All patients now are in disease free survival. No episode of acute graft versus host disease (GVHD) developed. It was concluded that HLA matched sibling allogeneic PBSCT result in rapid hematopoitic reconstitution and the MMC conditioning regimen is effective both in leukemic cells eradication and in immunosuppression for stem cells engraftment, and the drug related toxicity could be tolerated by patients. Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Semustine; Transplantation Conditioning | 1998 |
Busulphan and melphalan prior to autologous transplantation for myeloid malignancies.
We report our experience with 67 patients with myeloid malignancies (acute myeloid leukaemia (AML) or chronic myelogenous leukaemia (CML) conditioned with busulphan and melphalan as preparation for autologous haemopoietic cell transplantation. The major non-haematological toxicities were severe mucositis, nausea and vomiting, but the marrow aplasia was delayed and of short duration. The anti-tumor effect was appreciable with subsequent chronic phase (CP) obtained in 30/31 CML in transformation and complete remission (CR) obtained in 2/3 refractory AML. Among 32 patients treated while they had no evidence of active disease, 12 remained in CR or CP with a median follow-up of 54.7 months. Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Busulfan; Combined Modality Therapy; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Male; Melphalan; Middle Aged | 1995 |
Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes.
As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor. Topics: Adolescent; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Busulfan; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Female; Humans; Infant; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Myelodysplastic Syndromes; Preleukemia; Remission Induction; Transplantation, Homologous | 1994 |
Amendment to clinical research projects. Genetic marking with retroviral vectors to study the feasibility of stem cell gene transfer and the biology of hematopoietic reconstitution after autologous transplantation in multiple myeloma, chronic myelogenous
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Breast Neoplasms; Cisplatin; Clinical Protocols; Combined Modality Therapy; Cyclophosphamide; Etoposide; Feasibility Studies; Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Melphalan; Multiple Myeloma; Neoplasm Metastasis; Retroviridae; Transfection; Transplantation, Autologous; Whole-Body Irradiation | 1993 |
Autologous blood stem cell transplantation followed by recombinant alpha interferon as treatment for patients with high-risk chronic myelogenous leukemia. A report of 32 cases.
Autologous blood stem cell transplantation (ASCT) was performed in 32 patients with high risk chronic myelogenous leukemia (CML). Prior to ASCT, the patients were given Busulfan and high-dose Melphalan. Peripheral blood stem cells collected at diagnosis were used to rescue hematopoiesis. Recombinant Interferon was administered after ASCT. In 24 patients transplanted in transformation, 23 achieved a complete hematological response and nine are still alive 9 to 73 months after ASCT. Eight other patients were transplanted in chronic phase for either the presence of bad prognostic factors (Sokal's classification) or no response to IFN. Seven are alive without transformation 16 to 48 months after ASCT. Although few patients presented a cytogenetical response (10/28), the survival observed in this series of patients compares favorably with that of patients treated conventionally. Thus, the place of ASCT in CML could now be tested prospectively. Topics: Adult; Blast Crisis; Blood Component Transfusion; Blood Transfusion, Autologous; Bone Marrow Purging; Busulfan; Combined Modality Therapy; France; Humans; Immunologic Factors; Interferon Type I; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Melphalan; Middle Aged; Prognosis; Recombinant Proteins; Risk; Survival Analysis; Treatment Outcome | 1993 |