Allogeneic stem-cell transplantation with sequential conditioning in adult patients with refractory or relapsed acute lymphoblastic leukemia: a report from the EBMT Acute Leukemia Working Party

Bazarbachi, Abdul-Hamid; Hamed, Rama Al; Labopin, Myriam; Afanasyev, Boris; Hamladji, Rose Marie; Beelen, Dietrich; Eder, Matthias; Scheid, Christof; Wu, Depei; Bunjes, Donald; Stepensky, Polina; Tischer, Johanna; Zina, Peric; Aljurf, Mahmoud; Giebel, Sebastian; Nagler, Arnon; Mohty, Mohamad

doi:10.1038/s41409-019-0702-2

Cited by 20 publications

(11 citation statements)

References 40 publications

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“…Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for various hematological malignancies. Chronic graft-vs.-host disease (cGVHD) is a leading cause of nonrelapse mortality after allo-HSCT (1)(2)(3)(4)(5). The clinical symptoms of cGVHD are highly variable, including skin sclerosis, bronchiolitis obliterans, salivary, and lacrimal gland pathology (6,7).…”

Section: Introductionmentioning

confidence: 99%

Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Yang

Chen

et al. 2020

Front. Immunol.

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Chronic graft-vs.-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that autoantibodies play an important role in the development of cGVHD. Anti-nuclear autoantibodies (ANA) is the most frequently detected autoantibodies in patients with cGVHD, but the role of anti-Ro52 autoantibodies (anti-Ro52) in cGVHD remains largely unknown. In this study, we analyzed autoantibodies from 84 patients after allo-HSCT, including 42 with active cGVHD and 42 without cGVHD. Autoantibodies were found in 36 (42.9%) patients. Among these autoantibody-positive patients, 28 (77.8%) patients had active cGVHD. The most frequent autoantibodies in patients with active cGVHD were ANA (50.0%), anti-Ro52 (28.6%) and anti-mitochondrial autoantibodies type 2 (4.8%). We further explored the association between anti-Ro52 and cGVHD. Patients with active cGVHD had higher anti-Ro52 levels than patients without cGVHD (P < 0.05). The increases of anti-Ro52 levels were more significant in patients with moderate/severe cGVHD compared to those of patients without cGVHD (P < 0.05). Stratified and multivariable logistic regression analysis demonstrated that moderate/severe cGVHD was an independent risk factor for the levels of anti-Ro52 (P < 0.01). ROC analysis confirmed anti-Ro52 as a risk factor for progression of skin cGVHD. Moreover, the anti-Ro52 levels were highly correlated with the levels of B cell-activating factor (BAFF) and IgG1 antibodies. Our study demonstrates that anti-Ro52 is associated with cGVHD. The increased levels of anti-Ro52 were associated with higher levels of BAFF and IgG1 antibodies, suggesting a mechanistic link between elevated anti-Ro52 levels and aberrant B cell homeostasis.

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Section: Introductionmentioning

confidence: 99%

Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Yang

Chen

et al. 2020

Front. Immunol.

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“…In the adult B-ALL population, the durability of response to CAR-T therapy alone has been poor compared with that in the pediatric B-ALL population. Adult r/r B-ALL carries a poor prognosis, with a median survival of less than a year; and less than half of these patients can receive allo-HCT, the only potentially curative modality in these settings (82,83). Table 3 summarizes the relapse rates and outcomes of r/r ALL after CAR-T therapy in multiple studies and compares the outcomes of adult patients who received post-CAR-T allo-HCT with those of patients who did not receive this therapy.…”

Section: Allo-hct After Car-t Therapy For R/r Adult Allmentioning

confidence: 99%

“…• Adult patients with r/r ALL can achieve unprecedented CR rates with CAR-T therapy and can be transitioned to allo-HCT. Previously, the rate of allo-HCT in r/r has been dismal at 10-30% in some studies (82). • Despite the use of various targets and costimulatory domains in various CAR constructs, the durability of remission achieved with CAR-T therapy alone in adult patients with r/r B-ALL has been poor, with relapse rates as high as 65-85% in various studies.…”

Section: Allo-hct After Car-t Therapy For R/r Adult Allmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cells in B-Acute Lymphoblastic Leukemia: State of the Art and Future Directions

et al. 2020

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Use of adoptive T-cell therapy modified with chimeric antigen receptor (CAR-T) has revolutionized treatment of patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). CART cells directed against CD19 antigen have produced response rates as high as 90% in clinical trials for r/r BALL. Despite high rates of complete remissions, the durability of responses has been sub-optimal with frequent relapses, especially in adult BALL population. Systemic toxicities from CART therapy and standardization of toxicities grading and management is another major hurdle in the development of CART field. In this review, we discuss the latest evidence of CART therapy in BALL , potential mechanisms of relapse and barriers to CART cell therapy in BALL. We also debate the role of allogeneic hematopoietic stem cell transplant (allo-HCT) post CART therapy.

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“…Some studies found that allogeneic hematopoietic stem cell transplantation (allo-HSCT) after anti-CD19 CAR-T therapy was associated with an improved leukemia-free survival (LFS) ( 8 – 10 ). Usually, after CAR-T cell therapy, patients undergo conditioning regimens such as myeloablative (cyclophosphamide and busulfan-based and total body irradiation-based) or nonmyeloablative regimens prior to allo-HSCT ( 11 , 12 ). However, this treatment protocol will lead to a relatively long treatment cycle and more adverse reactions for patients.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Successful engraftment of allogeneic hematopoietic stem cells using CAR-T cell therapy as the conditioning regimen in R/R Ph+ B cell acute lymphoblastic leukemia

et al. 2022

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BackgroundConsolidative allogeneic hematopoietic stem cells (allo-HSCs) after chimeric antigen receptor T cells (CAR-T) therapy is an emerging modality in hematologic malignancies. Knowledge about the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR-T therapy without a conditioning regimen is limited.Case presentationWe report a patient with relapsed/refractory (R/R) Ph+ B-cell acute lymphoblastic leukemia (ALL) who underwent anti-CD19 CAR-T immunotherapy. After 1 month of treatment, bone marrow hyperplasia remained reduced with no hematopoietic improvements. In line with this, allogeneic hematopoietic stem cells (HSCs) were extracted from an HLA-matched sibling donor and administered to the patient on day 33 after CAR-T cell therapy to support hematopoiesis. On day 40, the level of immature bone marrow lymphocytes was at 0% and minimal residual disease-negative, and the fusion gene BCR/ABL 190 was negative. Chimerism analysis showed full donor chimerism. Three months after CAR-T cells infusion, the patient was still in complete remission with full donor chimerism. However, decreased liver function with skin pigmentation and festering, indicative of acute graft versus host disease, was noted. The treatment was halted owing to financial reasons.ConclusionWe report the successful engraftment of allogeneic HSCs using CAR-T cell therapy as a conditioning regimen for R/R B-ALL patients.

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Allogeneic stem-cell transplantation with sequential conditioning in adult patients with refractory or relapsed acute lymphoblastic leukemia: a report from the EBMT Acute Leukemia Working Party

Cited by 20 publications

References 40 publications

Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Chimeric Antigen Receptor T-Cells in B-Acute Lymphoblastic Leukemia: State of the Art and Future Directions

Case Report: Successful engraftment of allogeneic hematopoietic stem cells using CAR-T cell therapy as the conditioning regimen in R/R Ph+ B cell acute lymphoblastic leukemia

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