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Objective: To analyse the results of allogeneic haematopoietic cell transplantation (HCT) in patients with advanced stages of Philadelphia chromosome-positive chronic myelogenous leukaemia (CML) who had previously been treated with imatinib mesylate (IM). Methods: We analysed the outcome of 61 patients with CML who had received allogeneic HCT from sibling ( n = 18) or unrelated ( n = 43) donors after having been treated with IM. Forty-one patients had received IM because of accelerated or blast phase CML. Conditioning therapy contained standard doses of busulfan ( n = 25) or total-body irradiation ( n = 20) in conjunction with cyclophosphamide in the majority of cases. Sixteen patients received dose-reduced conditioning with fludarabine-based regimens. Results: The incidence of grades II–IV and III–IV graft-versus-host disease was 66% and 38% respectively. The probability of overall survival (OS), disease-free survival (DFS) and relapse at 18 months for the whole patient cohort were 37%, 33% and 24% respectively. The probability of non-relapse mortality (NRM) at 100 d and 12 months was 30% and 46% respectively. Univariate analysis showed that fludarabine-based conditioning therapy, age ≥40 yr and >12 months interval between diagnosis and transplantation were associated with a significantly lower OS and DFS and a higher NRM. Conclusion: These data suggest that although pretreatment with IM is not an independent negative prognostic factor, it cannot improve the dismal prognosis of CML patients at high risk for transplant-related mortality. [ABSTRACT FROM AUTHOR]

Summary. Fifty-one adults with haematological malignancies were transplanted with CD34+ -selected peripheral blood progenitor cells (PBPC) from unrelated donors. The conditioning protocol contained total body irradiation (n = 17) or combinations of busulphan and other alkylating agents (n = 34). Antithymocyte globulin was infused in all patients. The median number of CD3+ T cells infused with the graft after purification with the Isolex 300® system in the first cohort of 18 patients was 2·1 × 105 /kg. Prophylactic donor lymphocyte infusion (DLI) containing 1 × 105 CD3+ T cells was performed on d 21 in the following 33 patients who had received PBPC purified by the CliniMACS® system. Early graft failure occurred in 8/51 patients (16%). After a median follow-up of 31 months (range 8–60), the probability of disease-free survival (DFS) was 36% for the whole group. Reasons for death were opportunistic infections (n = 15), graft-versus-host disease (GvHD, n = 7) and relapse (n = 4). Pre-transplant factors with significant impact on DFS were cytomegalovirus status and risk category of underlying disease. The occurrence of graft failure or GvHD was associated with poor outcome. Recipients of CD34+ -selected PBPC from unrelated donors are at high risk of infectious complications, relapse and graft failure which cannot be prevented by early reinfusion of unmodified donor lymphocytes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]