Evidence for a GVL effect following reduced-intensity allo-SCT in ALL: a British Society of Blood and Marrow Transplantation study

Medd, Patrick; Peniket, Andrew; Littlewood, Timothy; Pearce, Rachel; Perry, Julia; Kirkland, Keiren; Shaw, Bronwen E.; Potter, Mike; Craddock, Charles; Milligan, Donald; Fielding, Adele K.; Marks, David I.; Cook, Gordon

doi:10.1038/bmt.2012.261

Cited by 10 publications

(6 citation statements)

References 26 publications

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“…Even earlier withdrawal of prophylactic immunosuppression has so far not led to a significant manifestation of adverse immunological complications. However, antileukemic control with GVL reaction [20], the main goal of this post-transplant approach, was apparently maintained in most patients in spite of high-risk and even very high-risk ALL.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression could be an effective approach to patients with acute lymphoblastic leukemia

Raida¹,

Rusinakova²,

Szotkowska³

et al. 2015

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Presented are results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 13 patients with high-risk acute lymphoblastic leukemia (ALL) in the first complete remission after a reduced intensity conditioning combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg). The immunosuppressive effect of T-cell depletion reducing the risk of graft-versus-host disease (GVHD) and non-relapse mortality was compensated by early initiation of reduction and withdrawal of prophylactic immunosuppression aimed at maintaining effective immunological antileukemic control. The median post-transplant follow-up was 23 (range, 10-65) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute GVHD was observed in two cases (15.4%); the chronic form was not noted. Two patients (15.4%) relapsed with ALL at 3 and 16 months after transplantation. During the above post-transplant follow-up, all 13 recipients were alive, with a probability of 2-year disease-free survival of 76.9% (95% CI 51-100%). Although the results were obtained with a small pilot study group it may be assumed that, given the prognostic risk of most patients and the nearly 2-year median post-transplant follow-up, the approach may be considered as an alternative to HSCTs after traditional myeloablative or reduced conditioning regimens with standard GVHD prophylaxis.

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Section: Discussionmentioning

confidence: 99%

Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression could be an effective approach to patients with acute lymphoblastic leukemia

Raida¹,

Rusinakova²,

Szotkowska³

et al. 2015

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“…Previous studies [26,32,37,38,40,41,[66][67][68] also demonstrated that GVHD had a graft-versus-leukemia effect, but Grades III-IV aGVHD were accompanied by a higher NRM than cases without Grades III-IV aGVHD. [39,69] We also concluded that patients with Grades III-IV aGVHD had a higher NRM and poorer OS and LFS than those without Grades III-IV aGVHD, but there was no correlation with relapse.…”

Section: Discussionmentioning

confidence: 94%

“…Moreover, patients transplanted in ≥CR2 were more likely to be post-MRD positive than those in CR1 ( P = 0.016) in this study, which might be a reason why being in ≥CR2 was related to a higher CIR. Previous studies [ 26 , 32 , 37 , 38 , 40 , 41 , 66 – 68 ] also demonstrated that GVHD had a graft-versus-leukemia effect, but Grades III–IV aGVHD were accompanied by a higher NRM than cases without Grades III–IV aGVHD. [ 39 , 69 ] We also concluded that patients with Grades III–IV aGVHD had a higher NRM and poorer OS and LFS than those without Grades III–IV aGVHD, but there was no correlation with relapse.…”

Section: Discussionmentioning

confidence: 94%

“…For example, patients in the first complete remission (CR1) have better outcomes than those in CR2 or those with advanced disease stage. [26][27][28][29][30][31][32][33][34][35] Meanwhile, studies reported by others [26,28,32,[36][37][38][39][40][41][42][43][44] and us [45,46] have shown that the onset of graft-versus-host disease (GVHD) after allo-SCT can reduce CIR. Recent studies found that acute graftversus-host disease (aGVHD) or chronic graft-versus-host disease (cGVHD) could reduce CIR for patients with positive post-MRD [47] as well as for patients transplanted with advanced disease (≥CR3 or active disease).…”

Section: Introductionmentioning

confidence: 99%

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A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

Cao

Zhou

Liu

et al. 2021

Chinese Medical Journal

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Background For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. Methods A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. Results All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR ( P < 0.001, P = 0.004, and P < 0.001, respectively) and worse LFS ( P < 0.001, P = 0.017, and P < 0.001, respectively), and OS ( P < 0.001, P = 0.009, and P < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 ( P < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score. Conclusion This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

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“…Other forms of RRT were mild and less frequent. In spite of relatively low general non-hematological toxicity, reduced combination of fludarabine and "high-dose" melphalan had significant myelosuppressive and immunosuppressive potential that allowed to achieve a stable engraftment of donor hematopoietic and immunocompetent cells responsible for GVL effect [7,16].…”

Section: Discussionmentioning

confidence: 99%

Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression in patients with acute lymphoblastic leukemia – update of single center study

Raida¹,

Kuba²,

Rusinakova³

et al. 2017

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Presented are updated results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 25 adult patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) after a reduced intensity conditioning (RIC) combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg or recently 4.0 mg/kg) followed by early initiation of reduction and withdrawal of prophylactic posttransplant immunosuppression. The median post-transplant follow-up was 32 (range, 4-87) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute graft versus host disease (GVHD) as well as the chronic one were equally observed in four cases (16%). Five patients (20%) relapsed with ALL in the median of 9 (range, 3-15) months after HSCT. During the above post-transplant follow-up, 4 recipients (16%) died. Disease progression and posttransplant complications were the cause of death in three (12%) and one (4%) of them, respectively. The probabilities of 2-year event-free (EFS) and overall survival (OS) were 70.3% (95% CI 51.9-88.7%) and 86.1% (95% CI 71.6-100%), respectively. Presented study confirmed our previously reported promising results and this approach may be considered as an alternative to traditional HSCTs performed in high-risk patients with ALL.

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Evidence for a GVL effect following reduced-intensity allo-SCT in ALL: a British Society of Blood and Marrow Transplantation study

Cited by 10 publications

References 26 publications

Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression could be an effective approach to patients with acute lymphoblastic leukemia

Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression could be an effective approach to patients with acute lymphoblastic leukemia

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression in patients with acute lymphoblastic leukemia – update of single center study

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