melphalan and Leukemia-Lymphoma--Adult-T-Cell

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been accepted as a treatment option for aggressive (acute or lymphoma type) adult T cell leukemia/lymphoma (ATLL) patients with a poor prognosis, when a suitable HLA-matched donor is not available. However, haplo-HSCT carries a potential risk of treatment-related mortality including severe graft-versus-host disease (GVHD). Therefore, we conducted a prospective pilot study in order to evaluate the efficacy and safety of reduced-intensity haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with low-dose thymoglobulin (2.5 mg/kg only on day -2), fludarabine, melphalan, and total body irradiation 4 Gy for aggressive ATLL. Three consecutive acute type ATLL patients, who were ineligible for conventional myeloablative conditioning due to advanced age or comorbidities, were enrolled. One patient received pretransplant mogamulizumab therapy. All the patients were not in complete remission (CR) at the time of transplantation. Our transplantation protocol was safely carried out. CR was achieved in all the patients after transplantation. HTLV-I viral loads became undetectable after transplantation. No severe adverse events such as grade III-IV GVHD or viral/fungal diseases were observed. At a follow-up of 2 years, they were still in CR. However, T cell receptor repertoire diversities were low 1 year after transplantation in next-generation sequencing. Our results show encouraging therapeutic benefits of this pilot approach using reduced-intensity haplo-PBSCT with low-dose thymoglobulin for aggressive ATLL patients.

Topics: Aged; Allografts; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Female; Follow-Up Studies; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Time Factors; Transplantation Conditioning; Vidarabine; Viral Load; Whole-Body Irradiation

Attempts to improve the efficacy of pretransplant conditioning regimens have been published, the potential of a better antileukemic effect being impaired by more frequent and severe toxicities. The efficacy of an intensified regimen, TAM (TBI, high-dose cytosine arabinoside and melphalan), is evaluated by analyzing long-term follow-up of a homogenous group of 42 high-risk ALL patients allografted in first CR. Age at time of BMT was 25.9 +/- 10.4 years (3-41). Twenty-two patients had more than three adverse prognostic factors. Ten patients had a Ph chromosome. Probability of overall survival was 45 +/- 9%, and for all surviving patients median follow-up time was 66 months. Event-free survival was 40 +/- 8% at 7 years after transplantation and the expected relapse rate reached 31%. Twenty-two deaths occurred, six after a relapse but 16 appeared to be directly due to the BMT procedure. None of the pretransplant characteristics significantly affected outcome after BMT. TAM appeared to be an efficient antileukemic therapy for conditioning high-risk ALL patients before allogeneic transplantation, but was still very toxic. The use of TAM in adult ALL patients in first CR is not recommended and the real role of intensified conditioning regimens remains to be demonstrated.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Burkitt Lymphoma; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Female; Follow-Up Studies; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Melphalan; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Whole-Body Irradiation

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Drug Therapy, Combination; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Humans; Leukemia-Lymphoma, Adult T-Cell; Melphalan; Middle Aged