Subject(s)
Anemia, Aplastic/therapy , Hematopoietic Stem Cell Transplantation , Myeloablative Agonists/administration & dosage , Peripheral Blood Stem Cell Transplantation , Transplantation Conditioning , Vidarabine/analogs & derivatives , Adult , Anemia, Aplastic/complications , Anemia, Aplastic/mortality , Disease-Free Survival , Female , Follow-Up Studies , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/mortality , Humans , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation/mortality , Remission Induction , Retrospective Studies , Severity of Illness Index , Transplantation Conditioning/methods , Transplantation Conditioning/mortality , Vidarabine/administration & dosage , Whole-Body IrradiationABSTRACT
We initiated a randomized study of amifostine (the organic thiophosphate formerly known as WR-2721) given to patients during myeloablative conditioning therapy for allogeneic bone marrow transplantation. Amifostine was given at a dose of 1000 mg/day of conditioning and was well tolerated if attention was given to serum calcium levels, blood pressure and antiemetics. Since August 1998, 60 patients (30 on each arm) have completed the study. There was no significant difference in the days to neutrophil or platelet engraftment in either arm of the study. Significantly, the duration of grade I-IV mucositis was decreased in the group that received amifostine (P=0.02). Also grade III or IV infections (P=0.008), duration of antibiotic therapy (P=0.03) and duration of fever (P=0.04) were significantly reduced with amifostine. However, there were no differences in the incidence of grade III or IV mucositis, liver toxicity or renal toxicity. There were also no differences in early mortality, relapse and long-term survival. We conclude that amifostine, while reducing the duration of mucositis and infections (possibly through some preservation of gut mucosal integrity), has a modest effect in allogeneic bone marrow transplants given the multiplicity of factors influencing organ toxicity and survival in this setting.
Subject(s)
Amifostine/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Myeloablative Agonists/adverse effects , Adolescent , Adult , Amifostine/toxicity , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Graft Survival , Hematologic Neoplasms/complications , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Infections/etiology , Kidney Diseases/etiology , Kidney Diseases/prevention & control , Liver Diseases/etiology , Liver Diseases/prevention & control , Male , Middle Aged , Mouth Mucosa , Myeloablative Agonists/administration & dosage , Protective Agents/administration & dosage , Protective Agents/toxicity , Stomatitis/etiology , Stomatitis/prevention & control , Transplantation, Homologous , Whole-Body Irradiation/adverse effectsABSTRACT
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only known curative therapy for patients with chronic myeloid leukemia (CML), but is associated with significant morbidity and mortality. The recent introduction of imatinib mesylate (STI-571) and reduced intensity transplant regimens has made the choice of primary treatment for patients with CML increasingly difficult. We have evaluated the outcome of 53 patients who have received allogeneic HSCT from human leukocyte antigen (HLA)-identical sibling donors between October 1985 and March 2002, determined the variables affecting the outcome, and tried to define indications for this aggressive approach. Successful engraftment occurred in 49 (98%) of evaluable patients. Acute graft-versus-host disease (GVHD) of grade II to IV severity was observed in 63% of the evaluable patients whereas the incidence of chronic GVHD was 57.5%. The Kaplan-Meier estimate of survival at 10 years was 54% [95% confidence interval (CI): 38-70%] and 31% (95% CI: 6-56%) for patients with first chronic phase and more advanced diseases, respectively. Multivariate analysis showed that younger age, absence of grade III-IV GVHD, the use of busulphan and cyclophosphamide (BuCy) as preparative regimen, and transplantation performed after January 1992 were factors associated with improved survival. Patients who were 30 years of age or younger who had transplantation done within 1 year after diagnosis during their first chronic phase of disease had a particularly good prognosis, with a probability of surviving 10 years of 72% (95% CI: 52-92%). We conclude that allogeneic HSCT remains a feasible option for Asian patients with CML. The most favorable outcome is observed in younger patients with early phase of the disease.
Subject(s)
HLA Antigens/analysis , Hematopoietic Stem Cell Transplantation , Histocompatibility , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/surgery , Adolescent , Adult , Asian People , Cause of Death , Child , Child, Preschool , Feasibility Studies , Female , Follow-Up Studies , Graft vs Host Disease/epidemiology , Hematopoietic Stem Cell Transplantation/mortality , Humans , Incidence , Male , Neoplasm Recurrence, Local , Prognosis , Risk Factors , Survival AnalysisABSTRACT
The main obstacles to successful hematopoietic stem cell transplantation for patients with chronic myeloid leukemia (CML) in blast crisis (BC) are increased post-transplant relapse and high treatment-related mortality. We report a patient with CML in BC who was treated initially with imatinib mesylate and was then concurrently treated with a nonmyeloablative stem cell transplant. Successful engraftment of donor cells followed by complete cytogenetic remission was achieved in the absence of severe therapy-related toxicities. This case demonstrates that imatinib mesylate given through nonmyeloablative transplant is a minimally toxic therapeutic approach, which does not compromise engraftment and may result in a favorable outcome in patients with CML in BC.
