What are the steps and components involved in a bone‑marrow (stem‑cell) transplant, including pre‑transplant evaluation, donor selection, conditioning regimen, stem‑cell infusion, supportive care, and post‑transplant monitoring?

Bone Marrow (Stem Cell) Transplant: Key Components and Steps

Bone marrow transplantation involves a systematic process beginning with pre-transplant evaluation and HLA typing, followed by donor selection (prioritizing HLA-matched siblings), conditioning chemotherapy to ablate the recipient's marrow, stem cell infusion, and intensive supportive care with post-transplant monitoring for engraftment and complications. 1

Pre-Transplant Evaluation and Workup

Patient Assessment:

• Perform comprehensive diagnostic workup including peripheral blood and bone marrow examination with morphology, cytochemistry, immunophenotyping, and cytogenetic analysis 1, 2
• Conduct HLA typing of the patient and all family members immediately upon identifying transplant candidacy to enable prompt donor identification 1, 2
• Assess cardiac function with echocardiography in patients with risk factors or cardiac history before proceeding, as anthracyclines and conditioning regimens carry cardiac toxicity 1, 2
• Evaluate performance status, comorbidities, and organ function (pulmonary, renal, hepatic) as these predict transplant-related mortality 1
• Screen for active infections with blood cultures, urinalysis, and chest imaging, as infection is a leading cause of transplant-related death 3

Pre-Transplant Optimization:

• Initiate iron chelation therapy when serum ferritin exceeds 1000 μg/L to reduce transplant-related complications, though this can be deferred to post-transplant in upfront transplant cases 1
• Consider cytoreduction with hydroxyurea only within 6 weeks before transplant if white blood cell count exceeds 10,000/μL 1
• For patients with massive splenomegaly (>20 cm below costal margin), perform splenectomy, splenic irradiation, or JAK inhibitor therapy to reduce spleen size, as splenomegaly adversely affects engraftment 1

Donor Selection Algorithm

Donor Hierarchy (in order of preference):

1. HLA-matched sibling donors are the first choice for allogeneic transplantation 1
2. Matched unrelated donors (MUD) with 9-10/10 high-resolution HLA matching are second-line when no matched sibling exists 1
3. Haploidentical (half-matched) related donors are appropriate for high-risk patients or when MUD search would cause unacceptable delay 1
4. Cord blood transplantation is reserved primarily for pediatric patients when other options are unavailable 1

Critical Donor Selection Factors:

• Consider donor age and cytomegalovirus (CMV) serostatus when balancing non-relapse mortality versus relapse risk—younger matched unrelated donors may be preferable to older HLA-identical siblings 1
• Avoid haploidentical donors with donor-specific anti-HLA antibodies with median fluorescence intensity >10,000 1
• For haploidentical transplants, prioritize donors in this order: children, male siblings, father, siblings with non-inherited maternal antigen (NIMA) mismatch, siblings with non-inherited paternal antigen (NIPA) mismatch, mother, then other relatives 1
• Prefer ABO and CMV compatibility when multiple suitable donors exist 1

Stem Cell Source and Collection

Peripheral Blood is the Recommended Source:

• Peripheral blood stem cells are the preferred graft source for HLA-matched sibling and matched unrelated donor transplants 1
• Target higher CD34+ cell doses for unrelated donor transplants when feasible, though specific dose recommendations cannot be made due to limited data 1

Mobilization and Collection Process:

• Mobilize bone marrow stem cells into circulation using high-dose cyclophosphamide followed by filgrastim (granulocyte colony-stimulating factor) 4
• Collect stem cells from peripheral blood via leukapheresis after mobilization 5, 4
• Some centers perform ex vivo immunomagnetic selection to deplete lymphocytes from the graft 4
• Cryopreserve grafts until needed, with quality testing to ensure sterility and adequate stem cell content 4

Conditioning Regimen

Conditioning Intensity Selection:

• Choose conditioning intensity by balancing non-relapse mortality risk (higher with intensive regimens) against relapse risk (higher with reduced-intensity regimens) 1
• Conditioning regimens are classified as myeloablative, reduced-intensity, or non-myeloablative based on established criteria 1
• The specific conditioning protocol should account for patient age, performance status, comorbidities, disease risk, and donor type 1

Common Regimens:

• Standard induction for acute myeloid leukemia includes anthracycline (daunorubicin 60-90 mg/m² or idarubicin 12 mg/m² days 1-3) plus cytarabine 100-200 mg/m² continuous infusion days 1-7 ("7+3" regimen) 2
• Conditioning must ablate the recipient's marrow to create space for donor cells and provide immunosuppression to prevent graft rejection 5

Stem Cell Infusion

The Transplant Procedure:

• Infuse cryopreserved or fresh stem cells intravenously after completing the conditioning regimen 5, 4
• The infusion itself is relatively straightforward, resembling a blood transfusion 5
• Stem cells home to the bone marrow where they begin engraftment 6

Post-Transplant Supportive Care

Immediate Post-Transplant Period:

• Monitor for neutrophil engraftment (typically day 15-17 for bone marrow grafts, day 16 for peripheral blood) and platelet engraftment (typically day 24-29) 7
• Provide intensive supportive care including transfusion support, antimicrobial prophylaxis, and management of conditioning-related toxicities 3, 5
• Assess donor chimerism by day 28—target >95% donor CD3 chimerism as a marker of successful engraftment 7

GVHD Prophylaxis:

• Administer graft-versus-host disease prophylaxis, with post-transplantation cyclophosphamide commonly used for haploidentical transplants 7
• Monitor for acute GVHD (typically within first 6 months) and chronic GVHD (beyond 6 months) 7

Infection Surveillance:

• Screen for cytomegalovirus reactivation by day 100 (occurs in approximately 45% of patients) 7
• Monitor for Epstein-Barr virus and Human Herpesvirus-6 reactivation, with patterns varying by donor type 7
• Maintain high vigilance for bacterial and fungal infections during neutropenic period 3

Post-Transplant Monitoring and Follow-Up

Short-Term Monitoring:

• Perform serial peripheral blood counts to track hematopoietic recovery 1, 2
• Obtain bone marrow aspirates during aplasia to assess early marrow response or blast persistence 1
• Monitor for complete remission criteria: normal bone marrow cellularity, <5% blasts, morphologically normal hematopoiesis, and peripheral blood count recovery 2

Long-Term Surveillance:

• Continue monitoring for late complications including chronic GVHD, infections, organ dysfunction, and disease relapse 7
• Consider secondary transplants to evaluate long-term stem cell function in research settings 6
• Maintain psychosocial support, as inadequate preparation and support contribute to psychological difficulties 3

Treatment Setting Requirements:

• Perform transplantation only in specialized centers with full hematology/oncology services, bone marrow transplant unit, infectious disease expertise, adequate transfusion services, and psychosocial support 1, 2, 3
• Ensure all procedures meet national regulatory standards and international accreditation requirements 4