Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

Kevon Parmesar, Kavita Raj, Kevon Parmesar, Kavita Raj

Abstract

Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients.

Figures

Figure 1
Figure 1
Conditioning regimen used for nonmyeloablative haploidentical transplantation, using high dose cyclophosphamide (Cy) posttransplant for in vitro T cell depletion. Pretransplant conditioning involved Cy, fludarabine, and TBI, with administration of high dose Cy on day 3 (or days 3 and 4) after transplantation. GVHD prophylaxis consisting of tacrolimus and MMF was initiated after Cy. BMT: bone marrow transplantation, Cy: cyclophosphamide, TBI: total body irradiation, G-CSF: granulocyte colony stimulating factor, and MMF: mycophenolate mofetil.
Figure 2
Figure 2
Illustration of three types of NIMA-complementary HLA haploidentical stem cell transplants: A, B, and C. Transplantation from mother to offspring (A) causes a graft versus host (GVH) reaction against the inherited paternal antigen (IPA) and a host versus graft (HVG) reaction against the NIMA of offspring 1 (Mb). Transplantation from offspring to mother (B) causes a GVH reaction against the NIMA of offspring 2 (Ma) and HVG reaction against the inherited paternal antigen (IPA). Transplantation between NIMA-mismatched siblings with a shared IPA (C) involves bidirectional mismatch for the NIMA and bidirectional GVH/HVG reactions. Adapted from Ichinohe et al. [63].

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