Hematopoietic Cell Transplantation¶
Chapter 119 | Hematopoietic Cell Transplantation
KEY CLINICAL POINTS¶
- Hematopoietic cell transplantation (HCT) is used to treat nonmalignant and malignant lymphohematopoietic disorders by replacing abnormal marrow with donor cells.
- Graft-versus-host disease (GVHD) is a major complication, with acute GVHD occurring within 3 months and chronic GVHD developing 3–24 months post-transplant.
- HLA matching between donor and recipient is critical for reducing GVHD risk, with 1 in 4 full siblings being HLA-identical.
- Reduced-intensity conditioning regimens are preferred for older patients or those with comorbidities to minimize transplant-related mortality.
- Post-transplant complications include sinusoidal obstruction syndrome (SOS), infections, and immune reconstitution delays.
1. DEFINITION & OVERVIEW¶
Hematopoietic cell transplantation (HCT) involves replacing a patient's abnormal hematopoietic system with donor stem cells. It is used for nonmalignant disorders (e.g., immunodeficiencies) and malignancies (e.g., leukemia). HCT includes autologous (self-donor) and allogeneic (donor) transplantation, with allogeneic grafts conferring a graft-versus-tumor (GVT) effect.
Table 119-1: Probability of Identifying a Donor Based on Stem Cell Source and Patient Ethnicity¶
| Ethnicity | UNRELATED ADULT % | UNRELATED CORD % | HAPLOIDENTICAL % |
|---|---|---|---|
| Caucasian | 75 | 90 | >95 |
| Hispanic | 35 | 75 | 95 |
| Black | 18 | 70 | 90 |
1.1 Types of Transplantation¶
Autologous: Patient's own stem cells are used. No GVHD risk but lacks GVT effect. Allogeneic: Donor cells are used, with risks of GVHD and graft rejection. Syngeneic: Identical twin donors, no GVHD risk. Cord blood: Umbilical cord stem cells used for transplantation.
1.2 Stem Cell Sources¶
Bone marrow, peripheral blood, and umbilical cord blood are sources. Peripheral blood stem cells (PBSCs) are commonly used due to ease of collection.
2. EPIDEMIOLOGY¶
Global HCT rates vary with gross national income (GNI). Over 100,000 transplants performed in 2022. HLA matching is critical for reducing GVHD risk. HLA-identical sibling donors are most effective, with 1 in 4 full siblings being HLA-identical.
2.1 Risk Factors¶
HLA mismatch, older age, and prior chemotherapy increase GVHD risk. Reduced-intensity conditioning is used for older patients or those with comorbidities.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
GVHD occurs when donor T-cells attack recipient tissues. Graft rejection happens if recipient immune cells destroy donor grafts. HLA mismatching increases GVHD risk. Immunosuppressive regimens and T-cell depletion reduce these risks.
3.1 HLA Matching¶
HLA-A, -B, -C, and -D genes are critical for matching. HLA-identical siblings have 1 in 4 chance of matching. Haploidentical donors (1 haplotype match) are increasingly used with post-transplant cyclophosphamide.
4. CLINICAL FEATURES¶
Acute GVHD (within 3 months) presents with skin rash, liver dysfunction, and gastrointestinal symptoms. Chronic GVHD (3–24 months) resembles autoimmune disorders with mucosal and organ involvement. Post-transplant complications include infections, mucositis, and SOS.
Table 119-2: Clinical Staging and Grading of Acute Graft-Versus-Host Disease¶
| CLINICAL STAGE | SKIN | LIVER—BILIRUBIN, kmol/L (mg/dL) | GUT |
|---|---|---|---|
| 1 | Rash <25% body surface | 34–51 (2–3) | Diarrhea 500–1000 mL/d |
| 2 | Rash 25–50% body surface | 51–103 (3–6) | Diarrhea 1000–1500 mL/d |
| 3 | Generalized erythroderma | 103–257 (6–15) | Diarrhea >1500 mL/d |
| 4 | Desquamation and bullae | >257 (>15) | Ileus |
4.1 Acute GVHD¶
Skin rash, diarrhea, and liver dysfunction. Graded by severity (I–IV) using Table 119-2. Grades II–IV correlate with higher mortality.
4.2 Chronic GVHD¶
Autoimmune-like symptoms (malar rash, sicca syndrome, arthritis). 20–50% of allogeneic transplant recipients develop chronic GVHD.
5. DIFFERENTIAL DIAGNOSIS¶
Acute GVHD must be differentiated from infections (e.g., CMV, fungal infections), drug reactions, and other autoimmune conditions. Chronic GVHD overlaps with autoimmune disorders but is distinct in its clinical presentation and treatment.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis involves clinical evaluation, biopsy (skin, liver, gut), and HLA typing. Viral load testing (e.g., CMV PCR) and immune reconstitution monitoring are critical. Flow cytometry and fluorescence in situ hybridization (FISH) confirm engraftment.
6.1 Diagnostic Criteria¶
Acute GVHD diagnosed by skin, liver, or gut biopsy showing endothelial damage and lymphocytic infiltrates. Chronic GVHD diagnosed by clinical features and response to immunosuppression.
7. MANAGEMENT & TREATMENT¶
Immunosuppressive regimens (e.g., calcineurin inhibitors, mycophenolate mofetil) prevent GVHD. Graft failure is managed with growth factors and retransplantation. Steroid-resistant GVHD uses ruxolitinib or other JAK inhibitors. Infections are managed with prophylactic antibiotics and antifungals.
7.1 Conditioning Regimens¶
Myeloablative (e.g., busulfan, cyclophosphamide) for young patients. Reduced-intensity (e.g., fludarabine, low-dose total-body irradiation) for older patients or those with comorbidities.
7.2 GVHD Treatment¶
Acute GVHD: Prednisone, tacrolimus, or ruxolitinib. Chronic GVHD: Steroids, calcineurin inhibitors, or biologics (e.g., rituximab).
8. PROGNOSIS & COMPLICATIONS¶
5-year survival rates vary by disease: 95% for severe combined immunodeficiency, 98% for aplastic anemia, 95% for thalassemia. Complications include infection, organ toxicity (e.g., SOS), and long-term immune suppression.
Table 119-4: Estimated 3-Year Survival Rates Following Transplantation¶
| DISEASE | ALLOGENEIC, % | AUTOLOGOUS, % |
|---|---|---|
| Severe combined immunodeficiency | 95 | NA |
| Aplastic anemia | 98 | NA |
| Thalassemia | 95 | NA |
| Acute myeloid leukemia (first remission) | 57 | ID |
| Acute myeloid leukemia (second remission) | 53 | ID |
| Chronic myeloid leukemia (chronic phase) | 71 | NA |
| Chronic lymphocytic leukemia | 64 | NA |
| Multiple myeloma—initial therapy | NA | 80 |
| Hodgkin’s disease (first relapse/second remission) | 68 | 89 |
8.1 Long-Term Outcomes¶
Chronic GVHD may persist for years. Transplant-related mortality is 10–30% for severe SOS. Immunosuppression increases infection risk, requiring prophylaxis.
9. SPECIAL CONSIDERATIONS¶
Pregnancy is possible post-transplant but requires careful monitoring. Pediatric patients benefit from cord blood or haploidentical transplants. Elderly patients are managed with reduced-intensity regimens. Immunosuppression increases infection risk, requiring prophylaxis.
9.1 Pregnancy¶
Transplantation can occur before pregnancy, but immunosuppression may affect fetal outcomes. Counseling is essential.
10. KEY POINTS & CLINICAL PEARLS¶
- HLA matching is critical for reducing GVHD. 2. Reduced-intensity conditioning is preferred for older patients. 3. Acute GVHD is graded I–IV, with grades II–IV requiring aggressive treatment. 4. Chronic GVHD is managed with immunosuppression and biologics. 5. Prophylactic antibiotics and antifungals are essential post-transplant.