Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a complex multi-step therapy that involves preparative conditioning regimen (chemotherapy +/- total body irradiation) to suppress recipient immune system and create space in bone marrow, followed by infusion of donor hematopoietic stem cells (collected from peripheral blood with G-CSF mobilization, bone marrow harvest, or umbilical cord blood) that engraft and reconstitute the hematopoietic and immune systems. The therapeutic effect derives from both eradication of underlying disease by conditioning chemoradiotherapy and graft-versus-tumor (GVT) immune effect from donor T-cells recognizing residual malignant cells. Indications include high-risk acute leukemias (AML, ALL), MDS, myeloproliferative neoplasms (CML, myelofibrosis), CLL, lymphomas (Hodgkin, non-Hodgkin), multiple myeloma, severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, primary immunodeficiencies, hemoglobinopathies (sickle cell disease, thalassemia), and inherited metabolic disorders.
Donor selection is critical: HLA-matched sibling donor (MSD, 25% probability per sibling) is the preferred source with lowest GVHD risk; HLA-matched unrelated donor (MUD, found for 70-80% of Caucasians, lower for ethnic minorities) requires 10/10 or 8/8 HLA matching; haploidentical donor (HID, parent, child, or half-matched sibling, 99% probability of finding) using post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis has expanded access to transplantation; umbilical cord blood (UCB, can use less stringent HLA matching due to immunologic naivete but limited cell dose). Conditioning regimens are selected based on disease, age, comorbidities: myeloablative conditioning (MAC, e.g., busulfan-cyclophosphamide BuCy, total body irradiation TBI 12 Gy + cyclophosphamide) for younger fit patients with aggressive disease; reduced-intensity conditioning (RIC, e.g., fludarabine-melphalan FluMel, fludarabine-busulfan FluBu) for older or comorbid patients; non-myeloablative for elderly or very frail; sequential MAC (FLAMSA) for active disease.
GVHD prophylaxis includes calcineurin inhibitors (cyclosporine, tacrolimus) plus methotrexate for myeloablative HLA-matched transplants; post-transplant cyclophosphamide (PTCy) day +3 and +4 reduces GVHD in haploidentical and increasingly used in MUD/MSD transplants; mycophenolate mofetil (MMF) added for reduced-intensity. Anti-T-cell antibodies (ATG, alemtuzumab) for serotherapy in unrelated donor transplants. Acute GVHD (within 100 days) affects skin, liver, gastrointestinal tract; chronic GVHD (>100 days) is autoimmune-like multisystem disease. Major complications: graft failure (primary or secondary), GVHD (acute and chronic), infections (CMV, EBV, fungal, encapsulated bacteria, opportunistic), regimen-related toxicity (mucositis, hepatic veno-occlusive disease/sinusoidal obstruction syndrome, cardiomyopathy, pulmonary complications, secondary malignancies), and disease relapse. Long-term survivorship requires monitoring for chronic GVHD, secondary cancers, endocrinopathies, infertility, and cardiovascular disease.