Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia

Abstract

Summary:Allogeneic BMT is potentially curative for patients with acute myelogenous leukemia (AML) in first remission. However, many patients relapse after transplantation. Various immunotherapeutic options have been attempted with variable success in preventing relapse. Early identification of patients at high risk for relapse could allow prompt intervention. We examined the effect of slow lymphocyte recovery after siblingmatched allogeneic BMT on the risk of relapse in patients with AML. We also examined the effect of prednisone-containing GVHD prophylaxis on the rate of lymphocyte recovery. Patients with absolute lymphocyte count (ALC) Ͻ150 × 10 6 /l by day +30 had a 3.5-fold higher risk of relapse (P = 0.0088) and a lower overall survival (P = 0.0079) than patients with a higher ALC. We did not find correlation between lymphocyte count determined earlier in the post-transplantation course (day +21) and the risk of relapse. Patients receiving prednisone had a significantly lower ALC at day +30 than those who did not receive prednisone (289 vs 549 × 10 6 /l, P = 0.002). We conclude that a slow lymphocyte recovery after allogeneic BMT for AML is strongly predictive of subsequent relapse and that the type of GVHD prophylaxis should be considered when analyzing lymphocyte recovery. Bone Marrow Transplantation (2001) 28, 951-956. Keywords: allogeneic; bone marrow transplantation; cyclosporine; lymphocyte recovery; prophylaxis; relapse Allogeneic BMT offers the potential for cure in patients with acute myelogenous leukemia (AML). Several studies of allogeneic BMT have shown a benefit for patients in first remission with high-risk AML. [1][2][3][4][5] However, 10% to 40% of patients who have complete remission after allogeneic BMT for AML eventually relapse. Several factors, includ- ing FAB type, 6 associated karyotypic abnormalities, 7 stage of the disease, conditioning regimen used, 3,5 GVHD prophylaxis, 6 and development of acute and chronic GVHD, have been shown to influence the incidence of relapse after allogeneic BMT for AML. Therapeutic options are limited for those who relapse, as they tolerate further chemotherapy poorly, and repeat transplants have limited efficacy. 8,9 Immunotherapy offers a new approach to patients who relapse after allogeneic BMT. This has mostly been in the form of donor lymphocyte infusions (DLI), and several reports have demonstrated long-term survival with this approach. [10][11][12][13] These results have led to evaluation of its role in preventing relapse; however, DLI is also associated with a risk of severe GVHD. Other approaches for prevention of relapse have included the use of cytokines like interferon-alpha (IFN-␣) and interleukin-2 (IL-2) or rapid withdrawal of immunosuppression. Since only a quarter to a third of patients relapse after allogeneic BMT, a need exists for prognostic variables that can prospectively identify patients at risk for relapse and thereby help select appropriate patients for prophylactic immunotherapy.Slow recovery of the lymphocyte count after allog...

Long-term disease-free survival after nonmyeloablative cyclophosphamide/fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia

“…The fact that a significant fraction of patients experienced durable remissions (some of whom whose cGVHD resolved) argues in favor of GVL effects active in the early post transplant period; this interpretation agrees with Kumar et al, who suggest that slow lymphocyte recovery after matched-sibling allogeneic BMT for AML predicts subsequent relapse. [46][47][48][49][50] In fact, the overall relapse rate of 30.0% at 4.7 years is comparable to that observed with RIC regimens or conventional allotransplantation. 1,[51][52][53] The particularly low relapse rate with MUD transplants (9%) suggests that given sufficient immunosuppression to effect engraftment, the risk of progression/relapse after MUD transplantation may be more fundamentally susceptible to increases in GVHD preventive intensity than the relative strength of conditioning.…”

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning

“…4 Other studies have not demonstrated significantly improved immune reconstitution with RIC, 5,6 making this area a subject of continued debate (reviewed by Jimenez et al 7 ). While many previous studies of immune reconstitution post HSCT have focused on lymphocyte subset recovery, [8][9][10][11][12][13][14][15][16] we have previously shown that combined monocyte and lymphocyte recovery also has an impact on survival post myeloablative HSCT in acute leukemia due to a reduction in nonrelapse mortality. 17 Here, we test the hypothesis that both lymphocyte and monocyte recovery are similarly associated with survival in patients undergoing RIC allogeneic HSCT with fludarabine and melphalan.…”

Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia

“…[5][6][7] Previous studies have shown that delayed lymphocyte recovery post-allogeneic HSCT is associated with increased risk of relapse in acute myelogenous and lymphoid leukemia in adults. [8][9][10][11][12] The clinical induction of GVL effect offers a new approach for patients who relapse post-HSCT. 13 This has most commonly been as donor lymphocyte infusion (DLI), and several reports have demonstrated long-term survival with this approach.…”