allogeneic stem cell transplantation

Chronic lymphocytic leukaemia is the most common leukaemia in adults, and it remains an incurable malignancy with conventional chemoimmunotherapy. A middle-aged gentleman who was diagnosed with high-risk chronic lymphocytic leukaemia (CLL), Rai stage IV, Binet C with del(17p) and del(13q) underwent allogeneic haematopoeitic stem cell transplantation (allo-HSCT) from a human leukocyte antigen (HLA) identical sister. Allogeneic haematopoeitic stem cell transplantation remains the only treatment with curative potential but is associated with high non-relapsed mortality (NRM). The patient developed extensive skin, oral, and liver chronic graft versus host disease (GVHD) and required tacrolimus, mycophenolate mofetil (MMF), and prednisolone. In seventh month after allo-HSCT, the patient presented with systemic symptoms, right cervical lymphadenopathy, splenomegaly, marked pancytopaenia, and elevated lactate dehydrogenase (LDH). Bone marrow study, immunophenotyping (IP), chromosome analysis, and PET-CT scan confirmed relapsed CLL with no evidence of Richter’s transformation or posttransplant lymphoproliferative disease (PTLD). Withdrawal of immunosuppressant (IS) worsened cutaneous and liver GVHD. Chemotherapy was not a suitable treatment option in view of immunodeficiency. The patient underwent extracorporeal photopheresis (ECP) therapy eventually for extensive chronic GVHD, and the IS were gradually tapered to the minimal effective dose. The relapsed CLL was treated successfully with oral venetoclax accessible via a compassionate drug program. This case highlights challenges in managing relapsed CLL and loss of graft-versus-leukaemia (GVL) effect despite extensive chronic GVHD. Venetoclax is an effective and well-tolerated oral novel agent for relapsed CLL after allo-HSCT. In conclusion, this study achieved an excellent outcome when treating a patient with relapsed CLL after allo-HSCT using oral venetoclax and concomitant ECP therapy for extensive chronic GVHD. Venetoclax is a well-tolerated oral novel agent and long-term follow-up is important to ensure the disease achieves a sustained complete remission.

Author(s) Details:

Ching Soon Teoh
Haematology Unit, Department of Internal Medicine, Hospital Pulau Pinang, Jalan Residensi, 10990
Georgetown, Penang, Malaysia.

Ai Sim Goh
Haematology Unit, Department of Internal Medicine, Hospital Pulau Pinang, Jalan Residensi, 10990
Georgetown, Penang, Malaysia.


Also See : Comorbid Primary Biliary Cholangitis and Systemic Lupus Erythematosus : A Part from the Book Chapter : Association of Systemic Lupus Erythematosus and Primary Biliary Cholangitis


Recent Global Research Developments in Graft-Versus-Host disease (GVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

GvHD and Relapse/Rejection-Free Survival (GRFS) in Severe Aplastic Anemia:

  • A comprehensive analysis from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation included 479 patients with idiopathic SAA who underwent allo-HSCT.
  • The study focused on two cohorts: upfront allo-HSCT from a matched related donor (MRD) and allo-HSCT for relapsed or refractory SAA.
  • Key findings:
  • Upfront MRD allo-HSCT: Achieved a 5-year GRFS of 77%. Early allo-HSCT in younger patients with an MRD was associated with favorable outcomes.
  • Relapsed/Refractory SAA cohort: Had a 5-year GRFS of 61%. Age was a significant risk factor for death, acute GvHD, and chronic GvHD as causes of GRFS failure [1].

Impact of GVHD on Pediatric Leukemia HSCT:

  • A retrospective analysis of pediatric leukemia cases in Japan revealed insights into GVHD following allogeneic HSCT. The study aimed to understand the advantages and disadvantages of GVHD [2].

Functional Impact of Chronic GVHD (cGVHD):

  • A review summarized evidence on how cGVHD affects function and discussed restorative interventions [3].

Haploidentical HSCT and GVHD Outcomes:

  • Investigating 938 patients who received haplo-HSCT using post-transplant cyclophosphamide (PTCY), researchers assessed overall survival, relapse rate, and non-relapse mortality. GVHD significantly influenced transplant outcomes [4].

References

  1. Devillier, R., Eikema, D. J., Dufour, C., Aljurf, M., Wu, D., Maschan, A., … & De Latour, R. P. (2023). Graft-versus-host disease and relapse/rejection-free survival after allogeneic transplantation for idiopathic severe aplastic anemia: a comprehensive analysis from the SAAWP of the EBMT. Haematologica, 108(9), 2305.
  2. Kato, M., Kurata, M., Kanda, J. et al. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Bone Marrow Transplant 54, 68–75 (2019). https://doi.org/10.1038/s41409-018-0221-6
  3. Brothers, L., Malhotra, J., Andrews, C. et al. Graft-Versus-Host Disease: an Update on Functional Implications and Rehabilitation Interventions. Curr Oncol Rep 25, 145–150 (2023). https://doi.org/10.1007/s11912-023-01363-y
  4. Shimomura, Y., Komukai, S., Kitamura, T., Sobue, T., Akahoshi, Y., Kanda, J., … & Terakura, S. (2024). Effect of graft-versus-host disease on outcomes of HLA-haploidentical peripheral blood transplantation using post-transplant cyclophophamide. Bone Marrow Transplantation, 59(1), 66-75.

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