scholarly journals Practical Aspects of Allogeneic Hematopoietic Cell Transplantation for Patients with Poor-Risk Chronic Lymphocytic Leukemia

2011 ◽  
Vol 11 ◽  
pp. 161-172 ◽  
Author(s):  
Julio Delgado ◽  
Rafael F. Duarte
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Poor Risk ◽  
Gvhd Prophylaxis ◽  
Conditioning Regimens

Allogeneic hematopoietic cell transplantation has become a viable option for younger patients with poor-risk chronic lymphocytic leukemia. The results obtained with either conventional or reduced-intensity conditioning regimens have been recently evaluated and compared with alternative nontransplant strategies. This manuscript deals with practical aspects of the procedure, including patient and donor selection, conditioning regimen, GVHD prophylaxis, disease monitoring, infectious and noninfectious complications, and timing of the procedure. Finally, we speculate on how we could improve the results obtained with the procedure and new advances currently in clinical trials.

Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time?

Blood ◽  
2009 ◽  
Vol 114 (13) ◽  
pp. 2581-2588 ◽  
Author(s):  
Julio Delgado ◽  
Donald W. Milligan ◽  
Peter Dreger
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Number Of Patients ◽  
Conditioning Regimens ◽  
Reduced Intensity

AbstractThe development of reduced intensity conditioning regimens has increased the number of patients diagnosed with chronic lymphocytic leukemia that are referred for allogeneic hematopoietic cell transplantation (allo-HCT). However, given the toxicity of allo-HCT, it should only be offered to eligible patients whose life expectancy is significantly reduced by the disease. Accordingly, the European Group of Blood and Marrow Transplantation has recently identified those patients in whom allo-HCT could be a reasonable therapeutic approach. In this review, we have evaluated the outcome of chronic lymphocytic leukemia patients undergoing allo-HCT, either after conventional or reduced intensity conditioning regimens, in the context of current nontransplantation strategies. We have also analyzed the most important predisposing factors that might interfere with the procedure as well as posttransplantation complications that are particularly common in these patients. Finally, we have addressed the most relevant factors when deciding what patients should be considered for allo-HCT and the timing of the procedure.

The Effect of In Vivo T-Cell Depletion with Alemtuzumab on Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3014-3014
Author(s):  
Julio Delgado ◽  
Srinivas Pillai ◽  
Reuben Benjamin ◽  
Dolores Caballero ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Mixed Chimerism ◽  
Allogeneic Hct ◽  
Reduced Intensity

Abstract Reduced-intensity allogeneic hematopoietic cell transplantation (HCT) is increasingly considered as a therapeutic option for young patients with advanced chronic lymphocytic leukemia (CLL). We report 59 consecutive CLL patients who underwent allogeneic HCT following fludarabine and melphalan conditioning at four different institutions. For graft-versus-host disease (GVHD) prophylaxis, 38 patients (Cohort 1) received alemtuzumab (20–100 mg) and cyclosporine; and 21 patients (Cohort 2) received cyclosporine plus methotrexate or mycophenolate. Donors were 47 HLA-matched siblings and 12 unrelated volunteers, 6 of whom were mismatched. Median age at transplant was 53 (range, 34–64) years and median number of previous chemotherapy regimens was 3 (1–6), with 39% of patients being refractory to fludarabine. Nine patients had previously failed an autologous HCT. Fluorescent in-situ hybridization and IgVH mutation status data were available in 33 (56%) and 31 (53%) patients, respectively, being unfavorable (17p- or 11q-) in 22 (67%) and unmutated in 24 (77%) of them. All but 1 patient engrafted, and the median interval to neutrophil recovery (> 0.5 × 109/l) was 14 (range, 10–36) days. Twenty patients (34%), mostly from Cohort 1, received escalated donor lymphocyte infusions due to mixed chimerism or disease relapse. The overall complete response rate among 53 patients with measurable disease at the time of transplantation was 70%, whereas 21% had stable disease. Grade II-IV acute GVHD was observed in 14 (37%) and 12 (57%) patients from Cohorts 1 and 2, respectively (P = 0.17). Extensive chronic GVHD was observed in 3 (8%) and 10 (48%) patients from Cohorts 1 and 2, respectively (P < 0.01). The incidence of cytomegalovirus reactivation was not significantly different between cohorts (67% vs 47%, P = 0.23). With a median follow-up of 36 (range, 3–99) months for survivors, 18 (30%) patients have died, 3 of progressive disease and 15 of transplant-related complications. The 3-year overall survival (OS), progression-free survival (PFS) and non-relapse mortality were 66% (95% CI 48–84%), 38% (20–56%) and 21% (8–34%), respectively, for Cohort 1 and 65% (44–86%), 54% (32–76%) and 29% (10–48%) for Cohort 2 (P = 0.66; P = 0.33; and P = 0.53). Despite low patient numbers, alemtuzumab seemed particularly effective for unrelated donor recipients, with a 3-year OS and PFS of 54% and 40% for Cohort 1; and 33% and 0% for Cohort 2 (P = 0.02 and P = 0.07). In conclusion, results with reduced-intensity allogeneic HCT are promising for these poor-prognosis patients. Furthermore, the alemtuzumab-based regimen was effective in reducing the chronic GVHD rate with no negative effect on NRM, PFS or OS.

OUTCOME of Allogeneic Hematopoietic CELL TRANSPLANTATION for AML: A Single CENTER Retrospective ANALYSIS.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4567-4567
Author(s):  
Ioanna Sakellari ◽  
Chrisa Apostolou ◽  
Despina Mallouri ◽  
Anastasia Athanasiadou ◽  
Ioannis Batsis ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Cytogenetic Analysis ◽  
Hematopoietic Cell Transplantation ◽  
Risk Group ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Intermediate Risk ◽  
Term Survival ◽  
Poor Risk

Abstract Abstract 4567 Background: Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for patients (pts) suffering of AML with high risk features at diagnosis and beyond 1st complete remission (CR1) it remains the sole rescue treatment. In this retrospective study we analysed the data of all pts (149) allografted concecutively in our BMT unit for AML from 1991 to 2009. The aim of the study was to estimate the outcome in terms of overall survival (OS), disease free survival (DFS), relapse rate (RR) and non relapse mortality (NRM). Sixty-three pts of a median age 35 (8-63) years suffered from de novo (58), secondary (4) and biphenotypic AML (1) were transplanted in CR1. Cytogenetic analysis was available in 40/63 pts (intermediate 32, poor risk 8). Donors were siblings in 55, relative (1 antigen mismatch) in 3, unrelated (4 mismatched with 1–2 alleles) in 8 pts. Graft source was bone marrow (BM) in 12 and peripheral blood (PB) in 51 pts. Fifty-six received a myeloablative (MA) and 7 non- myeloablative (NMA) conditioning regimen. Eighty-six pts were allografted beyond CR1. Disease status was primary refractory (Prim. Ref) in 42/86, CR2 in 15, 1st refractory after re-induction relapse (Rel1) in 23 and advanced (CR3; Rel2+) in 6 pts. Three pts were retransplanted from the original donor for relapsed disease after alloHCT. In the cohort of pts with disease beyond CR1, cytogenetic analysis was available in 71 (favourable 4, intermediate 53, poor risk 14). Donors were siblings in 58, syngeneic (1 antigen mismatch) in 8, unrelated (3 with mismatch) in 17, unrelated double cord blood (CB) in 1, haploidentical in 5 pts. The majority of the pts received mobilized PB (72) as graft source and myeloablative conditioning regimen (82). Results: For pts transplanted in CR1 OS was 63%, NRM 23%, DFS 60% and RR 21% at 13 years. Seventeen pts transplanted before 2000 had an estimated OS and DFS 59%, RR 9% and NRM 35% whereas for forty-six pts transplanted after 1999 the OS was 64%, DFS 61%, NRM 17% and RR 25% at 9 years. DFS for pts in CR1 with an unrelated donor was 47% and 62% for siblings. Myeloablative regimen resulted in 65% DFS while NMA in lower DFS (21%) due to higher RR. According to cytogenetics OS and DFS were 62% and 64% for the intermediate risk group (n=32), 44% and 45% for the poor risk (n=8) respectively. For the cohort of pts transplanted for Prim. Ref. disease (n=42) OS was 20% (plateau at 3 years), DFS 17% (plateau at 2 years), RR 78% and NRM 34% at 12 years. Despite the small number of pts with poor risk karyotype (n=7) the prognosis seemed to be dismal (DFS and OS 0%) versus 25% and 31% respectively for the intermediate risk group (n=28). For pts transplanted in CR2 (n=15) OS was 51% and DFS 46% (plateau at 1year), RR 43% and NRM 16%. For pts in REL1 (n=23) OS was 15%, NRM 56%, DFS 4% and RR 86%. For the 6 pts transplanted for advanced disease (CR3; REL2+) OS was 17%, DFS 17%, RR 67% and NRM 50%. The 5 pts undergone haploidentical alloHCT (2 Prim. Ref., 2 CR2, 1 CR3) after TBI 8/thiotepa/fludara/ATG had OS and DFS 40% at 8 years. One of 3 pts retransplanted is alive in CR and the rest succumbed to their disease. Discussion: In 2010 when the use of alternative transplantation has been expanted the selection of pts upon the best stratification and the timing of the transplantation still remain open questions. The majority of patients are classified in the intermediate risk group with normal karyotype. According to our experience during the last two decades alloHCT for AML in early disease phase (CR1) can offer the best results and possibly cure in a significant number of patients (60%). Transplantation procedures have been continuously improved over time leading to improvement of the outcome mostly in the era of alternative donor alloHCT. For poor risk pts in CR1 and for all pts with AML beyond CR1 (apart from acute promyelocytic leukemia in molecular remission) alloHCT remains the only treatment option. In this cohort of pts results from our data indicate that pts in CR2 may attain long term survival after alloHCT (OS 51%, NRM 16%). Among pts refractory to induction and salvage treatment therapies (> CR2, Prim Ref., REL) a small proportion of pts (15-20%) may be rescued by alloHCT. Disclosures: No relevant conflicts of interest to declare.

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