Chronic lymphocytic leukaemia (CLL) is now recognised as a heterogenous disease with a variety of clinical outcomes. It is the most common leukaemia in adults, and it remains an incurable malignancy with conventional chemoimmunotherapy. It is a rare type of cancer that affects the blood and bone marrow. Approximately 80% of CLL patients have cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH). CLL is characterised by the clonal expansion of mature, CD5 positive, B lymphocytes in the blood, marrow, lymph nodes and spleen. Detection of high-risk cytogenetic is important because it is associated with advanced disease, chemotherapy resistance, and inferior survival. To date, there are three new orally available pathway inhibitors approved for relapsed or refractory CLL: Bruton’s kinase inhibitor, ibrutinib, the phosphatidylinositol 3-kinase (PI3K) inhibitor, idelalisib, and the B-cell lymphoma 2 (BCL-2) inhibitor, venetoclax. However, it is costly and not widely available in public hospitals. Allogeneic haematopoeitic stem cell transplantation (allo-HSCT) remains the only treatment with curative potential but is associated with high non-relapsed mortality (NRM). Therefore, only selected patients with high-risk disease should be considered for allografting. These poor prognostic markers include del(17p), TP53 mutation, del(11q), complex cytogenetic abnormalities, and unmutated IgVH genes. Remarkable improvement in patient outcomes has been achieved through reduced intensity conditioning (RIC) allo-HSCT for patients with CLL. There was less toxicity and NRM compared to myeloablative conditioning (MAC). CLL is a malignancy with a well-established responsiveness to graft-versus-leukaemia (GVL) effects, and GVL activity has been reported in several studies using RIC regimens. Complete response and disease clearance were successfully demonstrated following donor lymphocyte infusion (DLI) given for persistent mixed chimerism. Besides, the onset of chronic graft versus host disease (GVHD) following RIC allo-SCT was significantly correlated with conversion from minimal residual disease (MRD) detectable to undetectable status. Although overall outcomes have improved significantly with the use of RIC allo-HSCT for high-risk CLL patients, 35-50% of patients will still experience disease relapse. Posttransplant relapse may be successfully managed by immunosuppressant (IS) withdrawal, DLI, combined chemotherapy, and DLI or clinical trials involving novel agents. Data on patients with relapsed disease after allo-HSCT are limited, as most clinical trials have excluded this subset of patients from enrolment. In this case report, we describe a challenging case of relapsed CLL despite extensive chronic GVHD successfully treated with oral venetoclax. There was a significant improvement in skin, oral, and liver GVHD after extracorporeal photo-pheresis (ECP) therapy. Some of the IS were tapered successfully to a minimal effective dose without exacerbation of GVHD.
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.
Recent Global Research Developments in Treatment for Chronic Graft-Versus-Host Disease
Understanding Chronic GVHD:
- Chronic GVHD is a significant cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HSCT).
- Symptoms are diverse, and standard treatments primarily involve corticosteroids.
- Advances in defining diagnosis, severity, and response criteria have occurred over the last two decades [1].
Biologic Mechanisms and Novel Therapies:
- Researchers have investigated the biologic mechanisms underlying cGVHD development.
- Promising immunomodulatory and targeted therapies are being explored.
- Multi-institutional collaboration and clinical trials have led to potential agents for cGVHD treatment [1].
Clinical Case Example:
- A 64-year-old male with relapsed acute myelogenous leukemia underwent allo-HSCT.
- He developed chronic GVHD symptoms (skin rash, dry eyes, dry mouth) after tapering immunosuppression.
- Treatment included tacrolimus, prednisone, and topical therapies.
- Adverse effects to steroids were managed, and successful tapering occurred [1].
References
- Hamilton, B. K. (2021). Updates in chronic graft-versus-host disease. Hematology, 2021(1), 648-654.
- Malard, F., & Mohty, M. (2023). Updates in chronic graft‐versus‐host disease management. American journal of hematology, 98(10), 1637-1644.