T-cell-depleted allogeneic transplant without donor leukocyte infusions results in excellent long-term survival in patients with multiply relapsed Lymphoma. Predictors for survival after transplant relapse

Abstract

We analyzed 67 patients with lymphoma who received alemtuzumab-based conditioning regimens for allogeneic stem cell transplant and no post-transplant DLI. The median age was 54 (24–70), 43% had unrelated donors, 34% had chemotherapy refractory disease, and 25% had an elevated LDH. With a median follow-up for survivors of 35 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 30% and 47%, respectively. Chemosensitivity by CT and pre-transplant LDH were independent prognostic factors for both overall survival and progression-free survival. Patient age, performance status, donor type, lymphoma subtype, disease sensitivity by PET, and conditioning regimen did not correlate with PFS and OS. Patients who relapsed greater than 6 months after allogeneic transplant were frequently able to re-enter a subsequent durable remission. Our experience confirms the curative potential of alemtuzumab-containing RIC regimens for allogeneic HCT in patients with relapsed lymphoma without prophylactic DLI. An elevated pre-transplant LDH and chemorefractory disease prior to transplant confer a worse prognosis, while PET scan findings do not have this same implication. Patients who relapse greater than 6 months after their transplant are likely to achieve a subsequent remission with any of a variety of interventions, suggesting that GVL effects can be operative even after recurrence. Our outcomes challenge the utility of the common practice of prophylactic DLI after T-depleted transplant for lymphoma.

A prospective study of an alemtuzumab containing reduced-intensity allogeneic stem cell transplant program in patients with poor-risk and advanced lymphoid malignancies

“…In univariate analysis, prior HDT-ASCT negatively impacted OS and PFS, elevated LDH at time of allo-SCT was prognostic for OS, and patients with HCT-CI ≥ 3 trended toward reduced OS and PFS (p=0.1). LDH above normal prior to allo-SCT has been previously identified by others to be a poor-prognostic feature in both alemtuzumab containing [32] and non- in vivo T cell depleted RIC allo-SCT [29]. HCT-CI ≥ 3 has reached prognostic significance in other RIC allo-SCT series for patients with lymphoid malignancies [33, 34].…”

Current status of allogeneic transplantation for aggressive non-Hodgkin lymphoma

“…Those who fail to respond to chemotherapy and come to transplant without radiologic response or with an elevated LDH are unlikely to do well; only a small fraction will be cured. 26;32;39;58;83;84 By contrast, several investigators find that findings of PET positivity have no impact for response to allogeneic transplant. 39;85 Patients with partial responses to salvage and normal LDH but residual PET positive areas may be good candidates for allogeneic transplant.…”

“…41;44 Avoidance of late chronic GVHD underlies our interest, and that of other groups in T-cell depleted transplant,usually using in vivo alemtuzumab or ATG. 36;38;39;45 Many studies, usually non randomized have compared the outcomes of T-depleted transplant and, with few exceptions have shown a somewhat increased rate of disease recurrence but no effect on survival. 46–48 Some studies, using profound in-vitro T-cell depletion have however shown a very high early recurrence rate.…”

“…57 Many recent large studies have a considerable number of unrelated donor recipients, who appear to have similar or even better outcomes than matched sibling transplants. 26;39;58–61 As donor typing becomes more accurate, it is also clear that many patients, particularly those of minority descent, lack matching donors. 62 Alternative donor transplant i.e.…”

“…Few if any such patients obtain durable remissions to further chemotherapeutic or immunologic intervention. 39;123–125 Occasional patients, particularly those with late relapses respond to further interventions and appear susceptible to GVL effects. Because of the poor progression of early relapsing patients, some have recommended pre-emptive therapy with DLI when mixed chimerism is observed.…”