melphalan and Anemia--Aplastic

Conditioning regimens for transplantation are important in determining transplant outcome. This review focuses on transplantation in aplastic anemia and leukemia using marrow from HLA-identical siblings. Results of conditioning with newer regimens such as busulfan plus cyclophosphamide and etoposide plus total body irradiation are reviewed and compared to results achieved with cyclophosphamide and total body irradiation. The potential for improved results using recent innovations such as dose adjustment of busulfan, agents which may decrease transplant-related toxicity, and directed radiation are discussed.

Topics: Anemia, Aplastic; Antilymphocyte Serum; Bone Marrow Purging; Bone Marrow Transplantation; Busulfan; Cyclophosphamide; Cytarabine; Etoposide; Humans; Leukemia; Lymphocyte Depletion; Melphalan; T-Lymphocytes; Transplantation, Homologous; Whole-Body Irradiation

Topics: Anemia, Aplastic; Antineoplastic Agents; Colony-Stimulating Factors; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Evaluation; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Melphalan; Neoplasms; Radiotherapy

Topics: Anemia, Aplastic; Benzene; Benzene Derivatives; Bone Marrow; Bone Marrow Cells; Chloramphenicol; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Melphalan; Mutation; Occupational Diseases; Oxymetholone; Phenylbutazone

Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years). At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA-matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other agents in 6 patients. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major cause of death was transplant-related complication (n = 9). Overall survival and event-free survival at 5 years after HSCT were both 41%. In summary, this study indicates that HSCT is a curative therapy for some patients with sMDS/sAML after aplastic anemia. Future efforts should focus on reducing transplantation-related mortality.

Topics: Adolescent; Adult; Anemia, Aplastic; Bone Marrow Transplantation; Busulfan; Child; Child, Preschool; Cyclophosphamide; Female; Graft vs Host Disease; HLA Antigens; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Melphalan; Myeloablative Agonists; Myelodysplastic Syndromes; Peripheral Blood Stem Cell Transplantation; Severity of Illness Index; Siblings; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous

Topics: Anemia, Aplastic; Clinical Trials as Topic; Cyclophosphamide; Drug Combinations; Evaluation Studies as Topic; Humans; Leukopenia; Melphalan; Middle Aged; Multiple Myeloma; Palliative Care; Prospective Studies; Radiography, Thoracic; Retrospective Studies; Thrombocytopenia

Topics: Adrenal Cortex Hormones; Allografts; Anemia, Aplastic; Antibodies, Monoclonal, Humanized; Antigens, CD19; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Deoxycytidine; Doxorubicin; Etoposide; Gemcitabine; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Oxaliplatin; Prednisone; Recurrence; Rituximab; Salvage Therapy; Transplantation, Autologous; Vincristine

Fludarabine/cyclophosphamide-based conditioning regimens are standard in bone marrow transplantation (BMT) for acquired bone marrow failure in children, however, graft failure may occur. Using the data from a nationwide transplantation registry, we compared the outcomes of children aged <16 years with acquired aplastic anemia and refractory cytopenia of childhood who underwent allogeneic BMT with either fludarabine/melphalan (n = 71) or fludarabine/cyclophosphamide (n = 296) between 2000 and 2016. The fludarabine/melphalan regimen provided excellent outcomes, with 3-year overall survival and failure-free survival rates of 98% and 97%, respectively. The 83% 3-year failure-free survival in the fludarabine/cyclophosphamide group was significantly inferior (P = 0.002), whereas the overall survival did not differ between the two groups. Late graft failure was the most common cause of treatment failure in the fludarabine/cyclophosphamide group, which experienced a significantly higher incidence of late graft failure than the fludarabine/melphalan group (11% vs. 3%; P = 0.035). Multivariate analyses showed that the fludarabine/melphalan regimen was associated with a better failure-free survival (hazard ratio [HR] 0.12; P = 0.005) and lower risk of late graft failure (HR 0.16; P = 0.037). Fludarabine/melphalan-based conditioning regimen can be a promising option for children with acquired bone marrow failure receiving BMT.

Topics: Anemia, Aplastic; Bone Marrow Transplantation; Child; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Transplantation Conditioning; Vidarabine

Allogeneic hematopoietic stem cell transplantation is the treatment of choice in young patients with severe aplastic anemia. The main causes of failure after this procedure are graft versus host disease, infections and graft failure, often exacerbated by large numbers of transfusions and prolonged disease duration before transplant.. We report the results of allografting following conditioning with fludarabine, alemtuzumab and melphalan in: five patients with severe aplastic anemia and one with hypoplastic myelodysplastic syndrome. All patients had matched sibling donors. Source of hematopoietic stem cell was: bone marrow-2, blood-3, bone marrow and blood-1. The age of recipients was 18-26 years. Four patients received their graft as the first line therapy and two after failure of cyclosporine and antithymocyte globulin treatment. Number of transfused units including red blood cells and platelets before transplantation was 8-100 (median: 22) and 10-32 (median: 11), respectively. All donors and recipients were CMV-seropositive. Conditioning consisted of: alemtuzumab 30 mg/d (day -7 to -5), fludarabine 30 mg/m(2) (days -7 to -3) and melphalan 140 mg/m(2) at the day -2.. The time to granulocytes and platelets recovery was 15 and 25 days, respectively. All patients achieved full donor chimerism on day +60. Only two patients needed ganciclovir as preemptive therapy. Recurrent parvovirus B19 infection with pure red cell aplasia and acute viral B hepatitis was observed in one case. Pure red cell aplasia was successfully treated with immunoglobulins and cyclosporine discontinuation. With a follow-up of 16-39 (median: 29) months all patients are alive, and neither graft failure nor graft versus host disease, or any no other severe complications, was observed.. Our study suggests that transplantation of hematopoietic stem cell using alemtuzumab, fludarabine and melphalan as a conditioning therapy is safe, inexpensive and effective treatment for patients with severe aplastic anemia, including multi-transfused adults having their disease for a long time.

Topics: Adolescent; Adult; Alemtuzumab; Anemia, Aplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Bone Marrow Transplantation; Costs and Cost Analysis; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Living Donors; Melphalan; Myelodysplastic Syndromes; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

Treatment of severe aplastic anemia (SAA) patients who lack human leukocyte antigen (HLA)-matched donors and failed immunosuppressive therapy (IST) is challenging. Recently, umbilical cord blood transplantation (CBT) after non-myeloablative therapy has been reported in adult but not in childhood SAA. However, most cases resulted in mixed donor chimerism and incomplete hematological recovery. We reported an 11-yr-old girl with recurred SAA 5 yr after IST who underwent unrelated donor CBT after a modified regimen. This patient had renal and cardiac dysfunction, and lacked suitable bone marrow donors. The 3.9 x 10(7)/kg CB cells from an HLA one-locus mismatched unrelated donor were infused after conditioning with total body irradiation (5 Gy), melphalan (120 mg/m(2)), and fludarabin (120 mg/m(2)). Hematological recovery was favorable in complete chimerism. A major complication was only skin graft-versus-host disease (grade I). CB could be an alternate stem cell source for childhood SAA after modified preparative regimen.

Topics: Anemia, Aplastic; Child; Cord Blood Stem Cell Transplantation; Female; Follow-Up Studies; Glucocorticoids; Graft vs Host Disease; Histocompatibility; Histocompatibility Testing; Humans; Melphalan; Myeloablative Agonists; Prednisolone; Severity of Illness Index; Time Factors; Transplantation Chimera; Transplantation Conditioning; Treatment Outcome; Vidarabine; Whole-Body Irradiation

A 10-year-old girl diagnosed with acute myeloid leukemia FAB M4 failed to achieve remission following several courses of induction chemotherapy. From the first course of chemotherapy the patient had continuous marrow aplasia, managed by a total of 57 granulocyte transfusions. After reinduction and reduced-intensity conditioning including fludarabine, Campath-1H, and melphalan, the patient received unmanipulated marrow from an HLA-matched unrelated donor. Leukocyte and platelet engraftment was observed on day +18 and +50, respectively. Graft-versus-host disease did not occur. The patient is alive and well in complete remission 18 months after transplantation with complete donor chimerism.

Topics: Alemtuzumab; Anemia, Aplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Female; Graft vs Host Disease; Granulocytes; Humans; Leukemia, Myelomonocytic, Acute; Melphalan; Neoplasm Recurrence, Local; Remission Induction; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

A 27-year-old man with aplastic anemia and renal insufficiency requiring dialysis underwent allogeneic PBSCT. The preparative regimen consisted of melphalan, ATG and TLI. GVHD prophylaxis consisted of cyclosporine and prednisolone. He was dialyzed prior to administration of melphalan and at 24 and 72 h after it. Otherwise, the dialysis schedule was unchanged, at three times a week. Engraftment was rapid. Regimen-related toxicity was minimal. Pharmacokinetic parameters of melphalan were not significantly altered with its plasma half-life 1.5 h. Patients with renal failure can receive allogeneic HSCT, and a combination of melphalan, ATG and TLI may serve as an alternative to CY and ATG.

Topics: Adult; Anemia, Aplastic; Antineoplastic Combined Chemotherapy Protocols; Cross Infection; Graft Survival; Graft vs Host Disease; Humans; Lymphatic Irradiation; Male; Melphalan; Peripheral Blood Stem Cell Transplantation; Renal Dialysis; Renal Insufficiency; Transplantation Conditioning; Transplantation, Homologous

Seventy-three BMT procedures (42 allogeneic-BMT, 30 autologous-BMT, 1 syngeneic transplant) were undertaken at the Shariati Hospital in Tehran between March 1991 and November 1993. Allogeneic-BMT was performed for thalassaemia major (n = 23), AML in complete remission (n = 3), severe aplastic anaemia (n = 7), CML (n = 7), dyskeratosis congenita (n = 2) and Fanconi anaemia (n = 1). Conditioning regimens comprised busulphan (BU) plus cyclophosphamide (CY) or CY only. Thirty-two (78%) of the 43 patients remain alive 1-34 months after BMT. Twelve patients died: the causes of death were haemorrhagic cystitis (n = 1), CMV pneumonitis (n = 1), GVHD (n = 3), infection (n = 3), rejection (n = 1), VOD (n = 2) and hepatitis (n = 1). Autologous-BMT was performed for patients with AML in CR (n = 16), ALL in CR (n = 9), lymphoma in relapse (n = 3), Ewing sarcoma (n = 1) and multiple myeloma (n = 1). The median age was 18 years. Conditioning regimens were Ara C plus CY, etoposide plus CY and high-dose melphalan. Sixteen (54%) of the 30 patients survive, 14 in continuous complete remission. The causes of death were relapse (AML (n = 7), ALL (n = 4), lymphoma (n = 1)), VOD (n = 1) and infection (n = 1).

Topics: Adolescent; Adult; Anemia, Aplastic; beta-Thalassemia; Bone Marrow Transplantation; Busulfan; Child; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Financing, Personal; Graft vs Host Disease; Humans; Insurance, Health, Reimbursement; Iran; Lymphoma; Male; Melphalan; Middle Aged; Transplantation, Autologous; Transplantation, Homologous

Several large cohorts of patients treated with alkylating agents served as a means to review the clinical and pathologic features of 55 cases of myelopathic disorders that resulted. The incidence was 1.8% overall and consisted of five patients (9.9%) who developed bone marrow hypoplasia or aplasia, 15 (27.2%) who developed a myelodysplastic syndrome, and 35 cases of acute myeloid leukemia (62.9%). The median time to recognition of MPD was 14 months, following cessation of chemotherapy. The distribution of the treatment-related MDS cases was different than "de novo" MDS with a high percentage of RAEB-T, and with the treatment related AMLs, there were a higher percentage of patients with FAB M6 (erythroleukemia), and no cases of FAB M3 (hypergranular promyelocytic). The median survival of all patients was very brief.

Topics: Adolescent; Adult; Aged; Alkylating Agents; Anemia, Aplastic; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Female; Gastrointestinal Neoplasms; Humans; Infant; Karyotyping; Leukemia, Myeloid, Acute; Male; Melphalan; Middle Aged; Myelodysplastic Syndromes; Ovarian Neoplasms