Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders.

We analyzed outcomes after hematopoietic cell transplantation (HCT) in 257 patients, 3 to 72.7 years old (median, 43 y), with secondary myelodysplastic syndrome (MDS) including those with transformation to acute myeloid leukemia (tAML). Conditioning regimens included high-dose total-body irradiation (TBI)/chemotherapy (n = 83); busulfan (BU)/cyclophosphamide (CY) (BUCY, n = 122; with BU targeting [tBUCY], n = 93); fludarabine (Flu) with tBU (FLUtBU; n = 12); Flu plus 200 cGy TBI (n = 26); and miscellaneous regimens (n = 14). Donors were HLA-identical or partially mismatched family members in 135 and unrelated individuals in 122 patients. Five-year relapse-free survival was highest (43%) and nonrelapse mortality lowest (28%) among tBUCY-conditioned patients. Outcomes were compared with results in 339 patients who received transplants for de novo MDS/tAML, and a multivariate analysis failed to show significant differences in outcome between the 2 cohorts. Relapse probability and relapse-free survival correlated significantly with disease stage (P < .001) and karyotype (P < .001). Relapse incidence was lower (P = .003) and relapse-free survival superior (P = .02) with unrelated donor transplants. The data suggest that overall inferior outcome in patients with secondary MDS/tAML was related to the frequency of high-risk cytogenetics. For both cohorts, transplantation outcomes improved over the time interval studied.

Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia.

The role of transplantation in infants with acute lymphoblastic leukemia (ALL) is not defined. We analyzed results of 40 infants diagnosed before age 12 months who received a hematopoietic cell transplant (HCT) between July 1982 and February 2003 in first complete remission (CR1; n = 17), CR2/3 (n = 7), or relapse (n = 16). Patients were conditioned with cyclophosphamide with total body irradiation (n = 39) or busulfan (n = 1). Donors were matched related (n = 8), mismatched related (n = 16), or unrelated (n = 16). Graft-versus-host disease (GVHD) prophylaxis was methotrexate or cyclosporine (n = 7) or methotrexate plus cyclosporine (n = 33). Thirty-nine patients engrafted, 20 developed acute GVHD, and 7 developed chronic GVHD. Sixteen patients relapsed and 7 died of other causes. Patients in CR1 had disease-free survival (DFS) of 76% compared with 45% for CR2/CR3 and 8% for relapse (P < .001). Of 33 patients with cytogenetic data, 26 (79%) had MLL gene rearrangement. Fourteen of these 26 were in CR1 and 11 survive in remission. Outcome was associated with phase of disease, but having the MLL gene was not a factor predictive of outcome. Late effects included growth and other hormone deficiencies. These data demonstrate that infants with ALL and MLL gene have excellent DFS when they received transplants in CR1, and consideration for transplantation in CR1 is warranted.

Predictors of relapse and overall survival in Philadelphia chromosome-positive acute lymphoblastic leukemia after transplantation.

Allogeneic transplantation offers a potential cure for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). We performed a retrospective analysis examining pretransplantation and posttransplantation prognostic factors in 90 patients with Ph+ ALL. The median age of the patients was 33 years, with slightly more than half of the patients (58%) in clinical remission at the time of transplantation. Overall, patients had a nonrelapse mortality rate of 30%, a relapse percentage of 34%, and an estimated 5-year disease-free survival rate of 30%. Pretransplantation risk factors for relapse included the expression of the p190 transcript (relative risk [RR] = 5.1; P =.037), evidence of morphologic disease at the time of transplantation (RR = 3.9; P <.001), and type of donor (RR = 2.5; P =.015), with patients receiving autologous or matched related transplants having the highest risk of relapse. The detection of minimal residual disease by reverse transcription polymerase chain reaction for bcr-abl transcripts was a significant posttransplantation risk factor for relapse (RR = 4.4; P =.001), with posttransplantation patients expressing the p190 transcript having the highest risk of relapse (RR = 8.7; P =.0001). In addition, patients with chronic extensive graft-versus-host disease showed a significantly lower risk of relapse (RR = 0.33; P =.038). Thus, these findings indicate that several pretransplantation and posttransplantation risk factors exist for patients with Ph+ ALL. Together, these factors can be used to improve our risk stratification of patients with Ph+ ALL who undergo transplantation, which will greatly enhance our ability to counsel these patients and potentially lead to the development of more specific treatment plans for them.

Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome.

A total of 109 patients (aged 6-66 years; median, 46 years) with myelodysplastic syndrome (MDS) were treated with busulfan (BU) targeted to plasma concentrations of 800 to 900 ng/mL plus cyclophosphamide (CY), 2 x 60 mg/kg, and hemopoietic stem cell (HSC) transplantation from related (n = 45) or unrelated donors (n = 64). At the time of transplantation, 69 patients had less than 5% myeloblasts in the marrow, and 40 patients had more advanced disease. All but 2 evaluable patients had engraftment. The Kaplan-Meier estimates of 3-year relapse-free survival (RFS) were 56% for related and 59% for unrelated recipients. The cumulative incidences of relapse were 16% for related and 11% for unrelated recipients. Nonrelapse mortality (NRM) at 100 days (3 years) was 12% (28%) for related and 13% (30%) for unrelated recipients. The only factor significant for RFS was the etiology of MDS (de novo better than treatment related; P =.03). Factors significantly correlated with relapse were advanced French-American-British classification (P =.002) and International Prognostic Scoring System score (P =.009), poor-risk cytogenetics (P =.03), and treatment-related etiology (P =.03). None of the factors examined was statistically significant for NRM. Patient age and donor type had no significant impact on outcome. RFS tended to be superior in patients receiving transplants with peripheral blood rather than marrow stem cells. Thus, a targeted BUCY regimen provided effective transplant conditioning for patients with MDS receiving transplants from HLA-identical siblings or alternative donors. Although there was still considerable nonrelapse morbidity and mortality, the present regimen was used successfully even in patients older than 60 years of age.