Non-myeloablative allogeneic stem cell transplantation using the combination of fludarabine/cyclophosphamide/rituximab as a conditioning regimen has been successful in treating patients with relapsed, chemosensitive non-Hodgkin’s lymphoma (

Blood
98
:
3595
,
2001
;
J Clin Oncol
21
:
4407
,
2004
). A more intense regimen however is required to have an early disease control for patients with refractory disease or in kinetic failure. We used the BEAM regimen for that purpose. Because of potential synergy and without overlapping toxicity, Rituximab (375 mg/m2 on days −6, −1, +7 and +14) was added to the preparative regimen. Transplantation was performed on day 0. Fourteen consecutive patients with refractory lymphoma or in kinetic failure were studied. The study group included 11 males and three females of median age of 46 (range, 19–60) yrs. Underlying histologies include diffuse large cell lymphoma (n= 9), follicular (n=1), mantle cell (n=1), lymphoplasmacytic (n=1), and CLL in Richter transformation to diffuse large cell (n=2). Median # of prior chemoregimens received was 3 (range, 1–8). Twelve patients had a matched sibling donor, one a mismatched sibling, and one a matched unrelated donor. The median # of CD34+ cells infused was 5 x 106 CD34 + cells/kg. Twelve patients received blood and 2 received marrow as the source of the hematopoietic graft. Tacrolimus and methotrexate were used for GVHD prophylaxis. The day-100 mortality was 7%. Eleven patients (79%) had a complete, and 2 (14%) had a partial remission. One patient (7%) had no response. All patients engrafted donor cells (median of 100% at day 30) post transplantation. Median time to ANC > 500 was 13 (11–15) days and median time to platelets > 20K was 14 (9–25) days. The actuarial risk of Gr 2–4 GVHD was 57%, Gr 3–4 GVHD 28%. Eleven of the 13 patients who were alive at day 100 developed chronic GVHD. With a median follow-up time among survivors of 34 (8–48) months, overall survival and disease-free survival were 63% (95% CI, 33–83) and 57% (95%CI, 28–78), respectively.

Our results indicate that a pronounced graft-versus-lymphoma occurs after BEAM/Rituximab and allogeneic transplantation for patients with refractory lymphoma or in kinetic failure. This treatment has been associated with a lower than expected treatment-related mortality and a higher chance of durable remission.

Topics:
conditioning (psychology), hodgkin's disease, lymphoma, rituximab, graft-versus-host disease, tissue transplants, transplantation, allogeneic stem cell transplant, cd34 antigens, cyclophosphamide

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2005, The American Society of Hematology
2004
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