Postulating favorable antileukemic effect with improved safety, we used intravenous busulfan and fludarabine as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Fludarabine 40 mg/m 2 and intravenous busulfan 130 mg/m 2 were given once daily for 4 days, with tacrolimus-methotrexate as graft-versus-host disease (GVHD) prophylaxis. We treated 74 patients with AML and 22 patients with MDS; patients had a median age of 45 years (range, 19-66 years). Only 20% of the patients were in first complete remission (CR) at transplantation. Donors were HLA-compatible related (n ؍ 60) or matched unrelated (n ؍ 36). The CR rate for 54 patients with active disease was 85%. At a median follow-up of 12 months, 1-year regimenrelated and treatment-related mortalities were 1% and 3%, respectively. Two patients had reversible hepatic veno-occlusive disease. Actuarial 1-year overall survival (OS) and event-free survival (EFS) were 65% and 52% for all patients, and 81% and 75% for patients receiving transplants in CR. Recipient age and donor type did not influence OS or EFS. Median
Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m 2 fludarabine, 4 g/m 2 cytarabine, and 36 mg/m 2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m 2 fludarabine and 140 or 180 mg/m 2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n ؍ 26) and AML (n ؍ 68) treated with FM (n ؍ 62) and FAI (n ؍ 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P ؍ .006), patients in first CR (28% versus 3%, P ؍ .008), and HLA-matched sibling donors (81% versus 40%, P ؍ .001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P ؍ .036), and lower cumulative incidence of relapse-related mortality (P ؍ .029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after
A new hematopoietic cell transplantationspecific comorbidity index (HCT-CI) was effective in predicting outcomes among patients with hematologic malignancies who underwent HCT at Fred Hutchinson Cancer Research Center (FHCRC). Here, we compared the performance of the HCT-CI to 2 other indices and then tested its capacity to predict outcomes among 2 cohorts of patients diagnosed with a single disease entity, acute myeloid leukemia in first complete remission, who underwent transplantation at either FHCRC or M. D. Anderson Cancer Center (MDACC). FHCRC patients less frequently had unfavorable cytogenetics (15% versus 36%) and HCT-CI scores of 3 or more (21% versus 58%) compared with MDACC patients. We found that the HCT-CI had higher sensitivity and outcome predictability compared with the other indices among both cohorts. HCT-CI scores of 0, 1 to 2, and 3 or more predicted comparable nonrelapse mortality (NRM) among FHCRC and MDACC patients. In multivariate models, HCT-CI scores were associated with the highest hazard ratios (HRS) for NRM and survival among each cohort.
Hematopoietic stem cell transplantation from unrelated donors is an effective treatment for myeloid malignancies, but its use is usually restricted to young patients without comorbidities. The development of reduced-intensity preparative regimens has allowed the extension of this form of treatment to older and medically infirm patients. We assessed the outcomes of patients older than 54 years who received unrelated donor transplants for the treatment of myeloid malignancies in our institution. There were 29 patients (median age, 59 years) with advanced acute myeloid leukemia (n ؍ 13), myelodysplastic syndrome (n ؍ 7), and chronic myeloid leukemia (n ؍ 9) included. With a median follow-up of 27 months, the probability of overall and event-free survival, and nonrelapse mortality at one year were 44%, 37%, and 55%, respectively. Grades II to IV acute graft-versus-host disease (GVHD) occurred in 41% of patients and chronic GVHD developed in 63% of patients surviving more than 100 days. Of the 11 survivors, 9 were interviewed and
Hemorrhagic cystitis (HC) remains a common complication of allogeneic blood and marrow transplantation. Previous analyses of risk factors for this complication were performed in heterogenous populations, with dissimilar diagnosis and conditioning regimens. We postulated that HC is more prevalent in matched unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in matched related donor (MRD) transplantations. We performed a retrospective study on 105 acute lymphocytic leukemia patients treated with 12 Gy total body irradiation-based regimens and allogeneic transplants (MUD, n ؍ 38; UCB, n ؍ 15; mismatched related, n ؍ 20; MRD, n ؍ 32). HC occurred in 16% of patients receiving MRD transplants, 30% of recipients of mismatched related, and 40% of MUD or UCB transplants (hazard ratio 2.9, 95% CI 1.0-7.9 for the comparison of MRD versus MUD). The excessive rate of HC among MUD and UCB patients became evident after the first 30 days after transplantation. Recipients younger than 26 years had a significantly higher incidence of HC (HR 2.5, 95% CI 1.1-5.8). This donor type and age effect was independent of platelet engraftment, development of graftversus-host disease (GVHD), source of stem cells, use of anti-thymocyte globulin (ATG) or cyclophosphamide in the regimen, steroid use, or stem cell source. We concluded that HC is more prevalent in MUD and UCB transplantations. (Blood.
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