Managing Bone Marrow Transplant
Guides BMT/SCT workflow from conditioning through engraftment monitoring and GVHD assessment.
Why This Skill Exists
Hematopoietic stem cell transplantation (HSCT) — including bone marrow transplant (BMT), peripheral blood stem cell transplant (PBSCT), and cord blood transplant — is the definitive curative therapy for many hematologic malignancies. The procedure carries treatment-related mortality of 10–30% depending on transplant type, conditioning intensity, and patient factors. FACT (Foundation for the Accreditation of Cellular Therapy) standards mandate comprehensive documentation of every phase from donor selection through long-term follow-up.
CIBMTR (Center for International Blood and Marrow Transplant Research) requires standardized outcomes reporting for all US transplant centers. GVHD remains the leading cause of post-transplant morbidity and mortality, requiring systematic grading and evidence-based management. Engraftment monitoring with chimerism testing informs critical decisions about immunosuppression tapering and donor lymphocyte infusion. Incomplete documentation or delayed recognition of complications leads to preventable mortality and regulatory non-compliance.
Checkpoint A: Pre-Draft Intake (Mandatory)
- What is the underlying diagnosis and disease status (CR1, CR2, primary refractory, relapsed)? (Default: [VERIFY])
- What type of transplant is planned (autologous, allogeneic — matched related, matched unrelated, haploidentical, cord blood)? (Default: specify)
- What conditioning regimen is planned (myeloablative, reduced-intensity, non-myeloablative)? (Default: specify)
- What is the GVHD prophylaxis regimen? (Default: specify)
- What is the patient's HCT-CI (Hematopoietic Cell Transplant Comorbidity Index) score? (Default: calculate)
- What is the donor information (HLA match, CMV status, ABO compatibility, sex match)? (Default: document)
- What is the patient's CMV, EBV, and HSV serostatus? (Default: document)
- What is the stem cell source (bone marrow, peripheral blood, cord blood) and target CD34+ cell dose? (Default: specify)
Documents to Request
- HLA typing results for patient and donor (high-resolution at HLA-A, -B, -C, -DRB1, -DQB1)
- Disease-specific risk assessment (Disease Risk Index)
- HCT-CI calculation worksheet
- Pre-transplant organ function assessment (pulmonary function tests, LVEF, LFTs, renal function)
- Infectious disease serologies (CMV, EBV, HSV, VZV, HBV, HCV, HIV, toxoplasma, syphilis)
- Pre-transplant disease restaging (bone marrow biopsy, imaging, MRD testing)
- Conditioning regimen protocol with dose calculations
- GVHD prophylaxis protocol
- Stem cell collection/product specifications (CD34+ dose, volume, cryopreservation details)
Step 1: Pre-Transplant Evaluation and Risk Assessment
HCT-CI scoring (Sorror et al.): Calculate comorbidity score (0 = low risk, 1–2 = intermediate, ≥3 = high risk):
| Comorbidity |
Score |
| Arrhythmia |
1 |
| Cardiac (LVEF ≤50% or prior MI or CHF) |
1 |
| Inflammatory bowel disease |
1 |
| Diabetes requiring treatment |
1 |
| Cerebrovascular disease |
1 |
| Psychiatric disturbance |
1 |
| Hepatic (mild: bilirubin ULN–1.5× or AST/ALT ULN–2.5×) |
1 |
| Obesity (BMI >35) |
1 |
| Infection requiring treatment at transplant |
1 |
| Rheumatologic disease |
2 |
| Peptic ulcer |
2 |
| Moderate/severe renal (CrCl <61) |
2 |
| Moderate pulmonary (FEV1 66–80% or DLCO 66–80%) |
2 |
| Prior solid tumor |
3 |
| Heart valve disease |
3 |
| Severe pulmonary (FEV1 ≤65% or DLCO ≤65%) |
3 |
| Moderate/severe hepatic (bilirubin >1.5× or AST/ALT >2.5×) |
3 |
Disease Risk Index (DRI): Low, intermediate, high, or very high — based on diagnosis and disease status at transplant. DRI stratifies expected relapse risk and overall survival post-transplant.
Step 2: Monitor Conditioning, Infusion, and Engraftment
Conditioning phase (Day -7 to Day -1):
- Administer conditioning per protocol with antiemetic prophylaxis
- Monitor for regimen-related toxicity (mucositis, hepatic VOD/SOS, cardiac toxicity from cyclophosphamide)
- Ensure adequate hydration for cyclophosphamide (mesna prophylaxis, forced diuresis)
Day 0 (Stem Cell Infusion):
- Document product identification, CD34+ cell dose infused, volume, viability
- Monitor for infusion reactions (DMSO-related for cryopreserved products: nausea, bradycardia, hypertension)
- ABO-incompatible transplants require product manipulation documentation
Engraftment monitoring (Day +1 to +30):
- Daily CBC with differential
- Engraftment defined as: ANC ≥500/μL for 3 consecutive days (neutrophil engraftment); platelet ≥20,000 for 7 days without transfusion (platelet engraftment)
- Median engraftment: PBSCT Day +12–14, BMT Day +18–21, Cord blood Day +24–28
- If ANC <500 by Day +28 (PBSCT) or Day +42 (cord blood): evaluate for graft failure — check chimerism, bone marrow biopsy
Step 3: Assess and Grade GVHD
Acute GVHD (typically within first 100 days):
| Organ |
Stage 1 |
Stage 2 |
Stage 3 |
Stage 4 |
| Skin |
Rash <25% BSA |
Rash 25–50% BSA |
Rash >50% BSA |
Generalized erythroderma with bullae |
| Liver |
Bilirubin 2–3 mg/dL |
Bilirubin 3.1–6 mg/dL |
Bilirubin 6.1–15 mg/dL |
Bilirubin >15 mg/dL |
| GI |
Diarrhea 500–999 mL/day |
Diarrhea 1000–1500 mL/day |
Diarrhea >1500 mL/day |
Severe abdominal pain ± ileus |
Overall acute GVHD grading (Glucksberg criteria):
- Grade I: Skin stage 1–2 alone
- Grade II: Skin stage 3, or liver/GI stage 1
- Grade III: Liver stage 2–3, or GI stage 2–3
- Grade IV: Skin stage 4, or liver/GI stage 4
Chronic GVHD (NIH Consensus Criteria): Assess 8 organ systems (skin, mouth, eyes, GI, liver, lungs, joints/fascia, genital tract). Score each 0–3. Classify overall severity as mild, moderate, or severe.
First-line treatment: Systemic corticosteroids (methylprednisolone 2 mg/kg/day for Grade II–IV acute GVHD). Steroid-refractory: ruxolitinib (FDA-approved for steroid-refractory acute and chronic GVHD).
Step 4: Manage Post-Transplant Complications and Monitoring
Infection prophylaxis schedule:
| Pathogen |
Prophylaxis |
Duration |
| Bacterial |
Fluoroquinolone (levofloxacin) |
Neutropenic period |
| HSV/VZV |
Acyclovir/valacyclovir |
Minimum 1 year; longer if on immunosuppression |
| PJP |
TMP-SMX or alternative |
Minimum 6 months; longer if on immunosuppression |
| Fungal |
Fluconazole or posaconazole |
Through neutropenic period; longer for GVHD patients |
| CMV |
Monitor by PCR weekly × 100 days; preemptive therapy with letermovir prophylaxis or valganciclovir if viremia detected |
Per institutional protocol |
| EBV |
Monitor by PCR; rituximab for PTLD |
Per institutional protocol |
Other critical monitoring:
- Chimerism testing (Day +30, +60, +100, then per protocol) — declining donor chimerism may indicate relapse or graft failure
- Bone marrow biopsy at Day +30 and +100 for disease assessment
- Hepatic VOD/SOS screening (weight, bilirubin, RUQ pain, fluid balance) — defibrotide for treatment
- Revaccination schedule beginning 6–12 months post-transplant per CDC/IDSA guidelines
Checkpoint B: Post-Draft Alignment (Mandatory)
- Is the transplant type, conditioning regimen, and GVHD prophylaxis completely documented?
- Are engraftment milestones tracked with dates of neutrophil and platelet engraftment?
- Is GVHD graded using standardized criteria (Glucksberg for acute, NIH Consensus for chronic)?
- Are infection prophylaxis and monitoring protocols documented per ASBMT/IDSA guidelines?
- Is chimerism testing scheduled and results documented with interpretation?
Quality Audit
Guidelines
- All allogeneic transplant patients require high-resolution HLA typing at a minimum of 5 loci (HLA-A, -B, -C, -DRB1, -DQB1)
- Engraftment failure workup should begin if ANC does not recover by Day +28 for PBSCT or Day +42 for cord blood
- Acute GVHD treatment should not be delayed pending biopsy confirmation — start empiric steroids for clinically suspected Grade II+ GVHD
- Steroid-refractory acute GVHD is defined as progression after 3 days or no improvement after 7 days of methylprednisolone 2 mg/kg/day
- CMV viremia monitoring must continue through Day +100 minimum, and longer for patients with GVHD on immunosuppression
- Declining donor chimerism in the T-cell compartment is an early warning of potential relapse — escalate with immunosuppression taper or DLI consideration
- Post-transplant relapse management depends on disease type, timing, and GVHD status — options include immunosuppression withdrawal, DLI, salvage chemotherapy, or second transplant
- Revaccination is required for all transplant recipients — prior immunity is not retained after myeloablative conditioning
1---2name: managing-bone-marrow-transplant3description: Guides BMT/SCT workflow from conditioning through engraftment monitoring and GVHD assessment. Use when managing transplant patients, monitoring engraftment, or assessing GVHD.4---56# Managing Bone Marrow Transplant78Guides BMT/SCT workflow from conditioning through engraftment monitoring and GVHD assessment.910## Why This Skill Exists1112Hematopoietic stem cell transplantation (HSCT) — including bone marrow transplant (BMT), peripheral blood stem cell transplant (PBSCT), and cord blood transplant — is the definitive curative therapy for many hematologic malignancies. The procedure carries treatment-related mortality of 10–30% depending on transplant type, conditioning intensity, and patient factors. FACT (Foundation for the Accreditation of Cellular Therapy) standards mandate comprehensive documentation of every phase from donor selection through long-term follow-up.1314CIBMTR (Center for International Blood and Marrow Transplant Research) requires standardized outcomes reporting for all US transplant centers. GVHD remains the leading cause of post-transplant morbidity and mortality, requiring systematic grading and evidence-based management. Engraftment monitoring with chimerism testing informs critical decisions about immunosuppression tapering and donor lymphocyte infusion. Incomplete documentation or delayed recognition of complications leads to preventable mortality and regulatory non-compliance.1516---1718## Checkpoint A: Pre-Draft Intake (Mandatory)19201. What is the underlying diagnosis and disease status (CR1, CR2, primary refractory, relapsed)? (Default: [VERIFY])212. What type of transplant is planned (autologous, allogeneic — matched related, matched unrelated, haploidentical, cord blood)? (Default: specify)223. What conditioning regimen is planned (myeloablative, reduced-intensity, non-myeloablative)? (Default: specify)234. What is the GVHD prophylaxis regimen? (Default: specify)245. What is the patient's HCT-CI (Hematopoietic Cell Transplant Comorbidity Index) score? (Default: calculate)256. What is the donor information (HLA match, CMV status, ABO compatibility, sex match)? (Default: document)267. What is the patient's CMV, EBV, and HSV serostatus? (Default: document)278. What is the stem cell source (bone marrow, peripheral blood, cord blood) and target CD34+ cell dose? (Default: specify)2829### Documents to Request3031- HLA typing results for patient and donor (high-resolution at HLA-A, -B, -C, -DRB1, -DQB1)32- Disease-specific risk assessment (Disease Risk Index)33- HCT-CI calculation worksheet34- Pre-transplant organ function assessment (pulmonary function tests, LVEF, LFTs, renal function)35- Infectious disease serologies (CMV, EBV, HSV, VZV, HBV, HCV, HIV, toxoplasma, syphilis)36- Pre-transplant disease restaging (bone marrow biopsy, imaging, MRD testing)37- Conditioning regimen protocol with dose calculations38- GVHD prophylaxis protocol39- Stem cell collection/product specifications (CD34+ dose, volume, cryopreservation details)4041---4243## Step 1: Pre-Transplant Evaluation and Risk Assessment4445**HCT-CI scoring (Sorror et al.):** Calculate comorbidity score (0 = low risk, 1–2 = intermediate, ≥3 = high risk):4647| Comorbidity | Score |48|------------|-------|49| Arrhythmia | 1 |50| Cardiac (LVEF ≤50% or prior MI or CHF) | 1 |51| Inflammatory bowel disease | 1 |52| Diabetes requiring treatment | 1 |53| Cerebrovascular disease | 1 |54| Psychiatric disturbance | 1 |55| Hepatic (mild: bilirubin ULN–1.5× or AST/ALT ULN–2.5×) | 1 |56| Obesity (BMI >35) | 1 |57| Infection requiring treatment at transplant | 1 |58| Rheumatologic disease | 2 |59| Peptic ulcer | 2 |60| Moderate/severe renal (CrCl <61) | 2 |61| Moderate pulmonary (FEV1 66–80% or DLCO 66–80%) | 2 |62| Prior solid tumor | 3 |63| Heart valve disease | 3 |64| Severe pulmonary (FEV1 ≤65% or DLCO ≤65%) | 3 |65| Moderate/severe hepatic (bilirubin >1.5× or AST/ALT >2.5×) | 3 |6667**Disease Risk Index (DRI):** Low, intermediate, high, or very high — based on diagnosis and disease status at transplant. DRI stratifies expected relapse risk and overall survival post-transplant.6869---7071## Step 2: Monitor Conditioning, Infusion, and Engraftment7273**Conditioning phase (Day -7 to Day -1):**74- Administer conditioning per protocol with antiemetic prophylaxis75- Monitor for regimen-related toxicity (mucositis, hepatic VOD/SOS, cardiac toxicity from cyclophosphamide)76- Ensure adequate hydration for cyclophosphamide (mesna prophylaxis, forced diuresis)7778**Day 0 (Stem Cell Infusion):**79- Document product identification, CD34+ cell dose infused, volume, viability80- Monitor for infusion reactions (DMSO-related for cryopreserved products: nausea, bradycardia, hypertension)81- ABO-incompatible transplants require product manipulation documentation8283**Engraftment monitoring (Day +1 to +30):**84- Daily CBC with differential85- Engraftment defined as: ANC ≥500/μL for 3 consecutive days (neutrophil engraftment); platelet ≥20,000 for 7 days without transfusion (platelet engraftment)86- Median engraftment: PBSCT Day +12–14, BMT Day +18–21, Cord blood Day +24–2887- If ANC <500 by Day +28 (PBSCT) or Day +42 (cord blood): evaluate for graft failure — check chimerism, bone marrow biopsy8889---9091## Step 3: Assess and Grade GVHD9293**Acute GVHD (typically within first 100 days):**9495| Organ | Stage 1 | Stage 2 | Stage 3 | Stage 4 |96|-------|---------|---------|---------|---------|97| Skin | Rash <25% BSA | Rash 25–50% BSA | Rash >50% BSA | Generalized erythroderma with bullae |98| Liver | Bilirubin 2–3 mg/dL | Bilirubin 3.1–6 mg/dL | Bilirubin 6.1–15 mg/dL | Bilirubin >15 mg/dL |99| GI | Diarrhea 500–999 mL/day | Diarrhea 1000–1500 mL/day | Diarrhea >1500 mL/day | Severe abdominal pain ± ileus |100101**Overall acute GVHD grading (Glucksberg criteria):**102- Grade I: Skin stage 1–2 alone103- Grade II: Skin stage 3, or liver/GI stage 1104- Grade III: Liver stage 2–3, or GI stage 2–3105- Grade IV: Skin stage 4, or liver/GI stage 4106107**Chronic GVHD (NIH Consensus Criteria):** Assess 8 organ systems (skin, mouth, eyes, GI, liver, lungs, joints/fascia, genital tract). Score each 0–3. Classify overall severity as mild, moderate, or severe.108109**First-line treatment:** Systemic corticosteroids (methylprednisolone 2 mg/kg/day for Grade II–IV acute GVHD). Steroid-refractory: ruxolitinib (FDA-approved for steroid-refractory acute and chronic GVHD).110111---112113## Step 4: Manage Post-Transplant Complications and Monitoring114115**Infection prophylaxis schedule:**116117| Pathogen | Prophylaxis | Duration |118|----------|-----------|----------|119| Bacterial | Fluoroquinolone (levofloxacin) | Neutropenic period |120| HSV/VZV | Acyclovir/valacyclovir | Minimum 1 year; longer if on immunosuppression |121| PJP | TMP-SMX or alternative | Minimum 6 months; longer if on immunosuppression |122| Fungal | Fluconazole or posaconazole | Through neutropenic period; longer for GVHD patients |123| CMV | Monitor by PCR weekly × 100 days; preemptive therapy with letermovir prophylaxis or valganciclovir if viremia detected | Per institutional protocol |124| EBV | Monitor by PCR; rituximab for PTLD | Per institutional protocol |125126**Other critical monitoring:**127- Chimerism testing (Day +30, +60, +100, then per protocol) — declining donor chimerism may indicate relapse or graft failure128- Bone marrow biopsy at Day +30 and +100 for disease assessment129- Hepatic VOD/SOS screening (weight, bilirubin, RUQ pain, fluid balance) — defibrotide for treatment130- Revaccination schedule beginning 6–12 months post-transplant per CDC/IDSA guidelines131132---133134## Checkpoint B: Post-Draft Alignment (Mandatory)1351361. Is the transplant type, conditioning regimen, and GVHD prophylaxis completely documented?1372. Are engraftment milestones tracked with dates of neutrophil and platelet engraftment?1383. Is GVHD graded using standardized criteria (Glucksberg for acute, NIH Consensus for chronic)?1394. Are infection prophylaxis and monitoring protocols documented per ASBMT/IDSA guidelines?1405. Is chimerism testing scheduled and results documented with interpretation?141142---143144## Quality Audit145146- [ ] HCT-CI score calculated and documented147- [ ] HLA matching documented at high-resolution for allogeneic transplants148- [ ] Conditioning regimen documented with dose calculations149- [ ] Stem cell product specifications recorded (CD34+ dose, viability, ABO compatibility)150- [ ] Engraftment dates documented (neutrophil and platelet)151- [ ] GVHD graded using standardized staging and overall grading152- [ ] GVHD treatment documented with steroid dose and taper plan153- [ ] Infection prophylaxis regimen documented per guidelines154- [ ] CMV monitoring schedule and results tracked155- [ ] Chimerism testing results documented with interpretation156- [ ] Disease restaging (Day +30, +100 bone marrow) documented157- [ ] Vaccination schedule initiated per IDSA/CDC guidelines158- [ ] CIBMTR reporting requirements met159- [ ] FACT standards compliance documented160161---162163## Guidelines164165- All allogeneic transplant patients require high-resolution HLA typing at a minimum of 5 loci (HLA-A, -B, -C, -DRB1, -DQB1)166- Engraftment failure workup should begin if ANC does not recover by Day +28 for PBSCT or Day +42 for cord blood167- Acute GVHD treatment should not be delayed pending biopsy confirmation — start empiric steroids for clinically suspected Grade II+ GVHD168- Steroid-refractory acute GVHD is defined as progression after 3 days or no improvement after 7 days of methylprednisolone 2 mg/kg/day169- CMV viremia monitoring must continue through Day +100 minimum, and longer for patients with GVHD on immunosuppression170- Declining donor chimerism in the T-cell compartment is an early warning of potential relapse — escalate with immunosuppression taper or DLI consideration171- Post-transplant relapse management depends on disease type, timing, and GVHD status — options include immunosuppression withdrawal, DLI, salvage chemotherapy, or second transplant172- Revaccination is required for all transplant recipients — prior immunity is not retained after myeloablative conditioning
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