scholarly journals Comparable long-term outcomes after reduced-intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high-risk acute lymphoblastic leukemia in complete remission

2013 ◽  
Vol 88 (8) ◽  
pp. 634-641 ◽  
Author(s):  
Ki-Seong Eom ◽  
Seung-Hwan Shin ◽  
Jae-Ho Yoon ◽  
Seung-Ah Yahng ◽  
Sung-Eun Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Long Term Outcomes ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Reduced Intensity

Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4439-4443 ◽  
Author(s):  
Mohamad Mohty ◽  
Myriam Labopin ◽  
Liisa Volin ◽  
Alois Gratwohl ◽  
Gérard Socié ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Retrospective Study ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Human Leukocyte ◽  
Myeloablative Conditioning ◽  
Leukocyte Antigen ◽  
Reduced Intensity

This retrospective study assessed the outcome of 576 adult acute lymphoblastic leukemia patients aged ≥ 45 years, and who received a reduced-intensity conditioning (RIC; n = 127) or myeloablative conditioning (MAC; n = 449) allogeneic stem cell transplantation (allo-SCT) from a human leukocyte antigen-identical sibling while in complete remission. With a median follow-up of 16 months, at 2 years, the cumulative incidences of nonrelapse mortality and relapse incidence were 29% ± 2% (MAC) versus 21% ± 5% (RIC; P = .03), and 31% ± 2% (MAC) versus 47% ± 5% (RIC; P < .001), respectively. In a multivariate analysis, nonrelapse mortality was decreased in RIC recipients (P = .0001, hazard ratio [HR] = 1.98) whereas it was associated with higher relapse rate (P = .03, HR = 0.59). At 2 years, LFS was 38% ± 3% (MAC) versus 32% ± 6% (RIC; P = .07). In multivariate analysis, the type of conditioning regimen (RIC vs. MAC) was not significantly associated with leukemia-free survival (P = .23, HR = 0.84). Despite the need for randomized trials, we conclude that RIC allo-SCT from a human leukocyte antigen-identical donor is a potential therapeutic option for acute lymphoblastic leukemia patients aged ≥ 45 years in complete remission and not eligible for MAC allo-SCT.

Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning (RIC) Is Effective for Long-Term Disease Control in High-Risk AML Patients in First Complete Remission.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3020-3020
Author(s):  
Philipp G. Hemmati ◽  
Gero Massenkeil ◽  
Theis H. Terwey ◽  
Stefan Neuburger ◽  
Philipp le Coutre ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Group Versus ◽  
Reduced Intensity Conditioning ◽  
Graft Versus Host ◽  
Significant Difference ◽  
First Complete Remission ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic stem cell transplantation (alloHSCT) is recommended for patients with high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Whereas conventional myeloablative conditioning is associated with a considerable treatment-related mortality (TRM), less intensive conditioning regimens may not be as efficient for long-term disease control, particularly in high-risk patients. Here, we present a retrospective single-institution analysis of 90 patients with median age of 39 years (range 17–66) with high-risk AML, i.e. based on non-favorable karyotype (not t(15;17), t(8;21) or inv(16)), blast persistence on day 16, the failure to achieve CR1 after two courses of induction therapy or the presence of secondary or therapy-induced AML, who underwent alloHSCT in CR1 between 1994 and 2007 (median follow-up 26, range 1–147 months). As stem cell source bone marrow (BM) was used in 17/90 patients (19%), whereas 73/90 patients (81%) received peripheral blood stem cells (PBSC). In 61/90 patients (68%) standard high-dose myeoloablative conditioning (12 Gy TBI + 120 mg/kg CY), (TBI group), was administered, whereas 29/90 (32%) patients received reduced-intensity conditioning (FLUD/BU/ATG)(RIC). A matched-related donor (MRD) was available for 62/90 patients (69%), whereas alloHSCT was performed from an unrelated donor (URD) in 28/90 patients (31%). Prevention of graft-versus-host disease (GvHD) consisted of CSA/MTX in the TBI group or CSA/MMF in the RIC group. 48/90 (53%) patients had a normal karyotype, whereas 39/90 patients (43%) displayed an aberrant karyotype. Projected overall survival (OS) and disease-free survival (DFS) of the whole cohort at 1, 3, and 5 years was 74%, 62%, and 57% and 72%, 58%, 54%, respectively. Causes of death were relapse (17/90 = 19%) or TRM (17/90 = 19%). The OS in the TBI group versus the RIC group was 72% vs. 79% at 1 year, 64% vs. 52 at 3 years, and 59% vs. 52% at 5 years (p = 0.78). Furthermore, there was no significant difference in the 1, 3, and 5-years DFS rates (72%, 62%, 57% vs. 75%, 50%, 49%) between the two groups. OS and DSF reached a plateau beyond 39 months (TBI group) and 33 months (RIC group). Relapse and TRM in the TBI group versus the RIC group were 21% vs. 14% and 16% vs. 24%. A comparison of the OS between the subgroups with a normal (n = 48) versus an aberrant (n = 39) karyotype revealed no significant difference at 1 year (83% vs. 65%), 3 years (70% vs. 47%), and 5 years (67% vs. 45%) (p = 0.06). Notably, there was no significant difference in the incidence of chronic graft-versus-host disease (cGvHD) between the TBI group and the RIC group (46% vs. 52%). Taken together, these results suggest that patients with AML in CR1 achieve a robust and durable long-term remission irrespective of the conditioning intensity (TBI vs. RIC) and the presence of an aberrant karyotype.

Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Acute Lymphoblastic Leukemia: Better Outcome in Transplantation during First Complete Remission and with Myeloablative Conditioning

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3295-3295
Author(s):  
Avichai Shimoni ◽  
Avital Rand ◽  
Izhar Hardan ◽  
Noga Shem-Tov ◽  
Anfisa Stanevsky ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Refractory Disease ◽  
Myeloablative Conditioning ◽  
Standard Risk ◽  
First Complete Remission

Abstract Allogeneic stem-cell transplantation (SCT) is potentially curative therapy in acute lymphoblastic leukemia (ALL). However, the timing of SCT during disease course and the prognostic factors for outcome are still under debate. We retrospectively analyzed all allogeneic transplants given for ALL over a 7-year period in a single institution. During this period we have used a uniform policy according to the GMALL protocols. Patients determined to be at high-risk at presentation were transplanted in the first complete remission (CR1) most often after first consolidation. Patients at standard risk at presentation were only transplanted after failure of induction or at relapse. Patients were transplanted from the best available donor and sibling donor availability was not a pre-request in any setting when referring to SCT. Patients considered eligible for myeloablative conditioning were given high-dose cyclophosphamide and TBI (12 cGy in 6 fractions). Patients considered non-eligible for myeloablative conditioning were given a reduced-intensity conditioning regimen (RIC) consisting of fludarabine and melphalan (total 140/m2). Patients with unrelated donors were also given ATG during conditioning. The study group included 81 patients, median age 40 years (range, 17–65). Immunophenotyping was B (n=31), T (n=48) and NK (n=2). Twenty-nine patients had high-risk cytogenetics [Ph+-24, t(4;11)-4, t(1;19)-1]. The donor was an HLA-matched sibling (n=48), matched unrelated (n=23), haplo-identical relative (n=8) and double umbilical cord blood (n=2). At the time of SCT, 36 patients were in high-risk CR1 (by the GMALL criteria), 12 were in CR after salvage therapy given for induction failure (CRIF), 13 patients were in CR2, and 20 patients were given SCT during active chemo-refractory disease. With a median follow-up of 27 months (range, 1–79), 31 patients are alive and 50 died (31 relapse, 19 non-relapse causes). Five patients are alive after relapse, all with isolated extra-medullary relapse (CNS-2, breast-1, bone-1, mediastinum-1). All patients with systemic relapse died of their disease. Overall and disease-free survival at 3 years were 33% (95CI, 22–44%) and 26% (95CI, 15–37%), respectively. The status of disease at SCT was the most important factor predicting for OS; the 3-year OS rates are 52%, 28%, 28% and 5% for patients transplanted in CR1, CRIF, CR2 and active disease respectively (p=0.0004). Donor type was also predicting for outcome in the univariable analysis; 3-year OS was 35%, 42% and 10% after sibling, unrelated and alternative donor transplants, respectively (p=0.04). OS rates after myeloablative conditioning and RIC were 37% and 20%, respectively (p=0.02). High-risk cytogenetics was not a risk factor for survival. Ph+ and Ph− patients had an OS of 38% and 30%, respectively, and when only analyzing patients in CR1, 48% and 53%, respectively (p=NS). Age, gender and immunophenotype were also not predicting for OS. Multivariable analysis identified two factors; SCT during CR1 was a favorable factor with HR of 0.3 (0.1–0.5, P=0.0005), while SCT with RIC was an adverse factor, HR 2.7 (1.4–5.2, P=0.004). Patients transplanted in high-risk CR1 with myeloablative conditioning had a 3-year OS of 55% (95CI, 36–75). In conclusion, best results are achieved in ALL in SCT during CR1. One can extrapolate that even better results may be expected in SCT in standard-risk ALL in CR1. Outcome after relapse and especially in chemo-refractory disease is poorer. RIC should only be used when there is an absolute contraindication for standard myeloablative conditioning.

scholarly journals Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2486-2496 ◽  
Author(s):  
Nathalie Dhédin ◽  
Anne Huynh ◽  
Sébastien Maury ◽  
Reza Tabrizi ◽  
Kheira Beldjord ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Key Points ◽  
First Complete Remission

Key Points SCT in first complete remission is associated with 69.5% 3-year overall survival in high-risk ALL adult patients treated with intensified pediatric-like protocol. Poor early MRD response is a powerful tool to select patients who may benefit from SCT in first complete remission.

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