Reduced intensity conditioning allows for up-front allogeneic hematopoietic stem cell transplantation after cytoreductive induction therapy in newly-diagnosed high-risk acute myeloid leukemia.

There is substantial need to improve the outcome of patients with high-risk acute myeloid leukemia (AML). The clinical trial reported here investigated a new approach of up-front allogeneic hematopoietic stem cell transplantation (HSCT), provided a median of 40 days (range 22-74) after diagnosis, in twenty-six consecutive patients with newly-diagnosed high-risk AML characterized by poor-risk cytogenetics (n = 19) or inadequate blast clearance by induction chemotherapy (IC, n = 7). The median age was 49 years (range 17-68). During IC-induced aplasia after the 1st (n = 11) or 2nd (n = 15) cycle, patients received allogeneic peripheral blood stem cells (PBSC) from related (n = 11) or unrelated (n = 15) donors following a fludarabine-based reduced-intensity regimen. Seventeen patients were not in remission before HSCT with a median marrow blast count of 34% (range 6-70). All patients achieved rapid engraftment and went into remission with complete myeloid and lymphatic chimerism. Grades II to IV acute GvHD occurred in 14 (56%) and extensive chronic GvHD was documented in 8 (35%) patients. The probability of disease-free survival was 61% with only three patients relapsing 5, 6 and 7 months after transplantation, respectively. Up-front allogeneic HSCT as part of primary induction therapy seems to be an effective strategy in high-risk AML patients and warrants further investigation.

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor.

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source of stem cells was blood in 102 patients, marrow in 10, and both in one. In total, 50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a median time of 13.5 and 13 days. The probabilities of event-free survival (EFS) (median follow-up: 12 months) were 49% for patients with less than 5% blasts in the marrow, 24% for patients with 5-20% blasts (P=0.002) and 14% with >20% blasts (P

Dose-reduced conditioning for allografting in 44 patients with chronic myeloid leukaemia: a retrospective analysis.

This retrospective study describes the outcome of patients with chronic myeloid leukaemia after allografting using dose-reduced conditioning with fludarabine and busulphan. Forty-four Philadelphia chromosome (Ph)-positive patients were transplanted in nine German centres; 26 patients were in chronic phase, 11 in accelerated phase and seven in blast crisis. Thirty-four patients achieved complete remission, with 18 alive and disease-free at a median follow-up of 562 d (range 244-922 d). Grade II-IV acute graft-versus-host disease (GVHD) incidence was 43%. Twenty patients died, 15 of causes unrelated to relapse. Risk factors predisposing to graft failure by univariate analysis were an unrelated donor (8/23 compared with a related donor 2/21, P = 0.07) and interferon therapy within 90 d of transplant (4/6 versus 3/17, P = 0.025). At the last follow-up, of 31 patients for whom molecular or cytogenetic data were available, 16 (52%) were polymerase chain reaction-negative, and seven (23%) were Ph-negative by fluorescent in situ hybridization. These findings demonstrate that dose-reduced conditioning with fludarabine and busulphan provides durable engraftment and a low rate of relapse. However, in this population, many of whom were not eligible for high-dose conditioning due to age, reduced performance status, previous complications or extensive pre-treatment, these data highlight the need for effective anti-infectious and GVHD prophylaxis. In addition, this study supports the discontinuation of interferon therapy at least 90 d before transplant

Allogeneic transplantation of G-CSF mobilized peripheral blood stem cells from unrelated donors: a retrospective analysis.

BACKGROUND AND OBJECTIVES: Allogeneic peripheral blood stem cell transplantation (PBSCT) from matched siblings has lead to clinical results comparable to those of standard bone marrow transplantation (BMT). We report the outcome of 79 patients transplanted with PBSC from unrelated donors. DESIGN AND METHODS: In 61 cases PBSC were used for primary transplantation whereas 18 patients were treated for relapse or graft-failure. In 35 patients receiving primary transplants, T-cell depletion (TCD) using CD34 positive selection of PBSC with or without additional T-cell depletion had been performed to reduce the risk of graft-versus-host-disease (GvHD). RESULTS: The rate of primary graft-failure was higher (20%) in the TCD group than in that receiving unmanipulated grafts (UM) (5%, p=0.007). Patients with standard risk (n=34) receiving first transplants had a significantly better overall (60.4% vs. 24%, p=0.02) and disease-free survival (57.2% vs. 22.3%, p=0.006) compared to a high risk group of patients (n=21). There were no differences in the speed of neutrophil and platelet engraftment between TCD and UM transplants. As expected, the cumulative risk for acute GvHD grade II.-IV was significantly higher in the patients who had received UM grafts (71.8% vs. 38.1%, p=0.005). Although a trend towards a better survival rate was observed after TCD transplantation (52.2%) compared to the UM group (38.1%), this difference was not statistically significant. The probability of relapse was significantly higher in patients after UM transplants (38.8% vs. 8. 4%). This apparent paradox is explained by the higher number of high-risk patients in this group (p=0.03). Multivariable analysis of disease-free survival revealed risk category (p=0.02) and use of ATG (p=0.03) to be of significant impact. All patients (n=6) with non-malignant diseases are alive with full donor chimerism. INTERPRETATION AND CONCLUSIONS: These data show that PBSC from unrelated donors can be transplanted either unmanipulated or CD34 selected. Prospective studies comparing BMT with PBSCT from unrelated donors are needed in defined disease categories.