scholarly journals Treatment of High-Risk Pre-B Acute Lymphoblastic Leukemia in a Fanconi Anemia Patient With Reduced-Intensity Chemotherapy

2013 ◽  
Vol 19 (2) ◽  
pp. S241 ◽  
Author(s):  
Ibraheem Abosoudah ◽  
Taher Sumaili ◽  
Mouhab Ayas
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Fanconi Anemia ◽  
Lymphoblastic Leukemia ◽  
Fanconi Anemia Patient ◽  
Anemia Patient ◽  
Reduced Intensity

Reduced-Intensity Allogeneic Peripheral Blood Stem Cell Transplantation for High-Risk Acute Lymphoblastic Leukemia: A Potential Therapeutic Approach for High Risk ALL Patients Not Eligible for Full Intensity Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4321-4321 ◽  
Author(s):  
A. Stein ◽  
J Palmer ◽  
M O’Donnell ◽  
N. Kogut ◽  
R Spielberger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Cancer Society ◽  
Full Intensity ◽  
Reduced Intensity ◽  
Donor Source

Abstract Acute lymphoblastic leukemia has a poor prognosis in adults, with a two-year survival rate of 35–40% despite aggressive therapy (American Cancer Society: Cancer Facts and Figures 2008 Atlanta, GA: American Cancer Society, 2008). Reduced-intensity allogeneic stem cell transplantation (SCT) relies mainly on graft versus leukemia (GVL) for its efficacy; however, the role of GVL in ALL is less well-defined. Between 5/7/02 and 6/15/07, 25 adult ALL patients were uniformly treated with fludarabine 25mg/m2 daily for 5 days and melphalan 140mg/m2 followed by ALLO-SCT using peripheral blood stem cells. The indications for the reduced intensity regimen were: ≥ 50 years (10 pts) (40%), decreased organ function (9 pts) (36%) and previous ALLO-SCT (6 pts) (24%). Patient demographics include: median age, 47 years (range, 23–68 yrs.), remission status at ALLO-SCT: first complete remission (CR) (12 pts) (48%), first relapse (3 pts) (12%), second CR (5 pts) (20%), >second CR (4 pts) (16%), induction failure (one pt) (4%), t(9;22) or Philadelphia positive (Ph+) ALL(9 pts) (36%). Donor source was matched sibling in 9 pts (36%), and matched unrelated in 16 pts (64%). Graft versus host disease (GVHD) prophylaxis: was cyclosporine (CSA)/+ mycophenylate (MMF) (3 pts) (12%), CSA/MMF/methotrexate (MTX) (8 pts) (32%), CSA/MMF/ATG (one pt) (4%), tacrolimus/sirolimus (7 pts) (28%) and tacrolimus/sirolimus/MTX (6 pts) (24%). With a median follow-up for surviving patients of 28.5 months (range: 12.8–72.5 months), the two year cumulative probability of overall survival and disease-free survival were both 59% (95% CI: 46–69.2%). The relapse rate was 16% (95% CI: 6.4,–37.4%),. Incidence of acute GVHD was 60% for grade II–IV and 20% for grade III–IV. Of the patients at risk for chronic GVHD, 8% developed limited chronic GVHD and 60% developed extensive chronic GVHD. The 100-day, one year and two year non-relapse mortality rates were 12% (CI: 4.6–29.3%), 24.2% (CI: 14–39.9%) and 29.3% (CI: 18.4–44.6%), respectively. There was no difference in survival outcomes based on donor source. The results of this study show that reduced intensity ALLO-SCT using fludarabine/melphalan based conditioning with primed peripheral stem cells from a matched related or unrelated donor provides a curative option for patients with high risk ALL who are not eligible for full intensity transplant. Figure Figure

Reduced Intensity Conditioning with Allogeneic Hematopoietic Cell Transplantation for the Treatment of High-Risk Acute Lymphoblastic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1210-1210
Author(s):  
Ron Ram ◽  
Rainer F. Storb ◽  
David G. Maloney ◽  
Brenda M. Sandmaier ◽  
Michael Maris ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
High Intensity ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity

Abstract Abstract 1210 Poster Board I-232 Allogeneic hematopoietic cell transplantation (HCT) with a conventional, high intensity conditioning regimen is an established approach for potentially curing patients (pts) with high-risk acute lymphoblastic leukemia (ALL). However, many pts are not candidates for high intensity conditioning HCT. The use of a reduced intensity conditioning (RIC) for ALL may provide an opportunity to decrease the toxicity of an intense conditioning regimen yet maintain the potential graft vs. leukemia effect. Here we describe the transplantation course and overall survival (OS) of 50 consecutive pts with high-risk ALL that were treated in a multi-center protocol of RIC and allogeneic HCT between February 2000 and August 2008. The median age was 56 (range, 7-69) years. All pts had cytogenetic analysis of bone marrow (BM) at diagnosis. 26 pts had Philadelphia chromosome positive (Ph+) ALL: 18 were in first complete remission (CR1) and 8 were in CR>1 at the time of HCT. 24 pts had Ph–ALL, 12 pts were in CR1 and 12 pts were in CR>1. Pts. were conditioned with fludarabine 90mg/m2 and 2 Gy total body irradiation. Nine pts received peripheral blood stem cells (PBSC) from HLA-identical siblings, 41 pts received grafts from unrelated donors (35 HLA-matched PBSC, 1 BM and 5 received 1-HLA-Ag mismatched PBSC). After the introduction of imatinib mesylate, 19 of the 26 pts with Ph+ALL participated in a study evaluating the safety and efficacy of imatinib starting at day +15 after HCT. Post-grafting immunosuppression consisted of combined mycophenolate mofetil and cyclosporine. Median follow up for surviving pts was 31 months (range, 12-91). One pt had graft rejection (BM recipient). 25 pts (50%) and 4 pts (8%) developed grades 2 and 3-4 acute graft-versus-host disease (GVHD), respectively. Chronic GVHD occurred in 24 pts (53% of pts surviving > 100 days); 15 pts (30%) developed extensive chronic GVHD. 19 pts (38%) relapsed at a median of 4.5 (range, 0.4-59) months. Non relapse mortality (NRM) at 2 and 5 years was 26% and 31%, respectively. Progression-free survival was very similar to OS. For all 50 pts, OS at 2 and 5 years was 37% and 27%, respectively. For pts in CR1 (n=30), OS was 52% and 41%, respectively. In contrast, OS for pts >CR1 (n=20) was significantly lower (13% and 7%, respectively, p=.003). For pts with Ph–ALL, OS was 29%, unchanged at both 2 and 5 years. Those in CR1 had improved OS compared with pts >CR1 (48% vs. 11% unchanged at both 2 and 5 years, respectively, p=0.07, Figure). OS for the 26 pts with Ph+ALL at 2 and 5 years was 45% and 27%, respectively. OS at 2 and 5 years for pts treated with imatinib after HCT was 52% and 43%, respectively, this was superior to the OS for pts with Ph+ALL that did not receive imatinib (p=0.03, Figure). For Ph+ALL pts in CR1 who had no evidence of minimal residual disease (MRD negative, detection by flow cytometry and FISH) prior to HCT and received imatinib (n=12), the OS was 67%, unchanged at both 2 and 5 years. In contrast, the pts with MRD negative Ph+ALL in CR1 who did not receive imatinib (n=4) had OS at 2 and 5 years of 50% and 0%, respectively. Imatinib after HCT was well tolerated: 3 pts required early stopping of imatinib due to associated reversible toxicity. We conclude that RIC with allogeneic HCT is a feasible treatment option that offers durable disease control, particularly for high-risk pts in CR1. The combination of post-transplant imatinib with RIC for Ph+ALL contributed to a substantially improved OS. Disclosures: Off Label Use: Imatinib - post-grafting treatment. Mycophenolate mofetil - immunosuppression after HCT.

scholarly journals 240: Reduced-intensity stem cell transplantation in patients with high-risk acute lymphoblastic leukemia (ALL)

2007 ◽  
Vol 13 (2) ◽  
pp. 88
Author(s):  
C.H. Gutierrez-Aguirre ◽  
G.J. Ruiz-Argüelles ◽  
O.G. Cantu-Rodriguez ◽  
O. Gonzalez-LLano ◽  
D. Gomez-Almaguer
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Reduced Intensity

scholarly journals Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2736-2743 ◽  
Author(s):  
Mitchell S. Cairo ◽  
Mary Gerrard ◽  
Richard Sposto ◽  
Anne Auperin ◽  
C. Ross Pinkerton ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Cns Involvement ◽  
Cns Disease ◽  
Non Hodgkin Lymphoma ◽  
Standard Intensity ◽  
Reduced Intensity

Abstract The prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined. Children 21 years old or younger with newly diagnosed B-cell non-Hodgkin lymphoma/B-cell acute lymphoblastic leukemia (B-NHL/B-ALL) with higher risk factors (bone marrow [BM] with or without CNS involvement) were randomized to standard intensity French-American-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 g/m2) plus extra intrathecal therapy. Fifty-one percent had BM involvement, 20% had CNS involvement, and 29% had BM and CNS involvement. One hundred ninety patients were randomized. The probabilities of 4-year event-free survival (EFS) and survival (S) were 79% ± 2.7% and 82% ± 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reduced-intensity therapy, the 4-year EFS after randomization was 90% ± 3.1% versus 80% ± 4.2% (one-sided P = .064) and S was 93% ± 2.7% versus 83% ± 4.0% (one-sided P = .032). Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide, Oncovin [vincristine], prednisone (COP) reduction therapy had a significantly inferior EFS and S (P < .001). Standard-intensity FAB/LMB therapy is recommended for children with high-risk B-NHL (B-ALL with or without CNS involvement).

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