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Reduced-intensity conditioning permits a significant graft vs leukemia (GvL) effect for acute leukemia

Year: 2006

Type: article

Abstract: Delivering effective treatment for acute leukemia to older adults remains a significant challenge. Bone marrow/hematopoietic progenitor cell transplant (HPCT) remains the only curative option for relapsed/refractory or unfavorable risk disease. Myeloablative conditioning regimens are associated with significant morbidity and mortality. The use of reduced intensity conditioning (RIC) may offer a chance for cure, but whether RIC allows for a significant GvL effect is unclear. We report a single institution follow-up of 21 adult patients with acute leukemia treated with peripheral blood HPCT following RIC after being deemed inadequate for fully myeloablative conditioning. A matched comparison arm of 42 consecutive patients transplanted after full myeloablative (FMA) conditioning is also reported. Methods: Between 1999–2004, 21 patients were treated with Fludarabine-based conditioning prior to infusion of hematopoietic stem cells. Patients were followed for toxicities and responses. IRB approval was obtained prior to data collection. Kaplan-Meier estimates of survival were performed. Patient disease characteristics were analyzed using T-tests to determine any factors that may be associated with outcome and relapse. Significant factors on univariate analysis were placed into a Cox regression model for multivariable analysis. Results: Patient characteristics: 76% of patients had AML and 24% had ALL. 14% of patients had relapsed or refractory disease at transplant. A greater proportion of patients undergoing RIC, had poor-risk cytogenetics. Median age was 56 yrs. 81% of patients experienced clinically significant acute or chronic GVHD. Overall post-transplant survival was 29%. Twenty-nine percent (6/21) patients suffered relapse at a median of 4 months post-transplant. Cox proportional hazards models for overall post-transplant survival and logistic regression models for relapse and overall survival (N = 63), showed that the only significant predictor for OS and relapse was cytogenetic risk group (P = .000). Of note, none of the 5 ALL patients transplanted after RIC have relapsed with a median follow-up of 2.2 years (0.1–3.9 years); among 16 AML pts., 5 have relapsed with median follow-up of 0.4 years (.1–2.2 years). These results compare favorably to our cohort of pts. transplanted after full myeloablative conditioning. Conclusion: The role of RIC transplants for the treatment of high risk acute leukemia in older adults remains a promising therapy and warrants further study (Table). Tabled 1Patient CharacteristicsCharacteristicsRIC pts. N = 21 (%)Comparison arm (FMA) N = 42 (%)ALL5 (24%)10 (24%)AML16 (76%)32 (76%)Median age56 (45–68)52 (41–62)Male14 (67%)20 (48%)Disease status at transplant:CR113 (62%)30 (71%)CR2–34 (19%)7 (17%)Relapsed-Refractory3 (14%)5 (12%)Donor: Related12 (57%)34 (81%)Unrelated9 (43%)8 (19%)Cytogenetic risk:⁎1 Pt, cytogenetics were unknownFavorable1 (5%)4 (10%)Intermediate6 (28%)19 (45%)Poor14 (76%)18 (43%) 1 Pt, cytogenetics were unknown Open table in a new tab

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2005.11.218