Allogeneic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukaemia: Local Results of Modern Transplant Practice.

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Abstract Aims: To report the single institution outcomes for recent allogeneic transplantation for adult acute lymphoblastic leukaemia (ALL), and explore variables predictive of successful outcome. Methods: All patients with ALL transplanted at the Royal Brisbane Hospital between 1st January, 2000 and 31st December, 2005 were included in the study sample. Survival analysis was performed using the Kaplan-Meier product-limit method. Univariate and multivariate analyses were performed using Cox proportional hazards modelling. Follow-up was censored at 30th June, 2006. Results: A total of 41 patients were included in the study cohort, including 28 males and 13 females. Median age at transplantation was 27.6 years (range 15.2 to 64.5). 34 patients had precursor-B phenotypes; the remaining 7 had T-lineage ALL. Based on cytogenetics, patients were high-risk (n=19), intermediate risk (n=12), good risk (n=2), or indeterminate due to inadequate diagnostic sampling (n=8). Patients were transplanted in CR1 (n=23, 2 patients demonstrating delayed CR), 1st relapse (n=5, 2 with early relapse, 1 with untested frank relapse, and 2 with refractory disease), CR2 (n=9, 2 with treated isolated CNS relapse), CR3 (n=1) and primary refractory disease (n=3). Conditioning regimen was CyTBI, with the exception of 1 patient who received fludarabine (125mg/m2) and cyclophosphamide (120mg/kg). All patients received cyclosporine and full-course methotrexate for GVHD prophylaxis. Donor source was matched sibling (n=17) and matched unrelated donor (n=24). 5 patients received unprimed bone marrow grafts; the remaining patients received peripheral blood stem cells. At a median follow-up for survivors of 1.8 years (range 0.5 to 6.4), overall and progression-free survival at 2 years is 61% (95% CI 43 to 75%) and 74% (95% CI 55 to 85%) respectively. 32 patients developed acute GVHD, of whom 27 (66%) developed Grades II–IV. 21/40 evaluable patients developed chronic GVHD; all were extensive stage. 9 patients relapsed during follow-up at a median of 0.47 years post transplant (range 0.02 to 1.46); 1 remains alive in remission following reinduction therapy. 6 patients died from therapy-related causes - 3 from pulmonary toxicity, and 1 each from fungal sepsis, leukoencephalopathy, and hepatic GVHD. On both univariate and multivariate analyses of overall survival, younger age, transplantation in CR1, and development of chronic GVHD were predictors for an improved outcome. Conclusions: Allogeneic stem cell transplantation for ALL is associated with excellent long-term outcome with respect to both disease control and treatment related toxicity. From these data, transplantation in CR1, younger age, and the development of chronic GVHD are covariates associated with prolongation of overall survival.

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