hematopoietic stem cell transplantation (HSCT)
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Introduction
Intravenous infusion of hematopoietic progenitor cells to establish bone marrow & immune function after ablation of host bone marrow.
Classification
Types of HSCT:
- autologous
- stem cell harvesting from patient prior to high-dose chemotherapy &/or radiation
- cryopreservation
- reinfusion into the patient after chemotherapy to restore hematopoiesis
- allogeneic
- HLA-matched donor
- HLA-identical sibling
- HLA-identical donor identified from the general population via searching international donor registries
- in some case, one antigen mismatch from a sibling may be tolerated
- allogeneic cells from fetal cord blood (rich in stem cells) may be associated with less graft-versus host disease
Phases post HSCT
- pre-engraftment phase 1 (< 30 days post HSCT)
- profound neutropenia distinguishes HSCT from other organ transplantation
- post-engraftment phase 2 (30-100 days post HSCT)
- late phase 3 (> 100 days post HSCT)
Indications
- hematopoietic malignancies
- aplastic anemia
- genetic blood disorders
- support for high-dose chemotherapy in which hematopoietic toxicity limits therapy (autologous HSCT)
Laboratory
- monitoring cytomegalovirus DNA with pre-emptive therapy preferred to prophylaxis with ganciclovir[1]
Procedure
allogeneic hematopoietic stem cell transplantation
- whole body irradiation
- myeloablative high-dose chemotherapy
- stem cell transplantation
- immunosuppressive therapy to prevent transplant rejection & graft-vs-host disease
Complications
- graft versus host disease (GVHD) (allogeneic HSCT)
- acute GVHD generally occurs within 3 months of transplantation
- chronic GVHD may occur with taper of immunosuppression
- risk of infection much greater after allogeneic HSCT than autologous HSCT because of myeloablative conditioning with a prolonged period of neutropenia & immunosuppression to suppress graft vs host disease[1]
- opportunistic infections
- pancytopenic phase 1 (< 30 days post transplantation)
- phase 2 (30-100 days post transplantation)
- cytomegalovirus pneumonitis (allogeneic HSCT)
- generally occurs within 3 months of transplantation
- Epstein-Barr virus*
- Staphylococcus epidermidis
- Candida
- invasive pulmonary aspergillosis
- Toxoplasma gondii*
- Strongyloides stercoralis*
- Pneumocystis jirovecii (late phase 2)
- cytomegalovirus pneumonitis (allogeneic HSCT)
- phase 3, late complications (> 100 days post transplantation)
- increased risk of infection with encapsulated organism
- cytomegalovirus pneumonitis
- bilateral diffuse interstitial infiltrates on chest radiograph[1][15]
- Varicella zoster reactivation (20-50%)
- dermatomal pain with vesicular rash
- disseminated vesicles with visceral involvement; liver, lung, brain
- Epstein-Barr virus*
- invasive pulmonary aspergillosis (most common in phase 2)[1][15]
- Pneumocystis jirovecii
- Toxoplasma gondii*
- BCNU-related interstitial pneumonitis with autologous HSCT
- Nocardia
- subacute onset, may or may not cause leukocytosis or fever
- much less common than Streptococcus pneumoniae[1]
- respiratory & enteric viruses (all phases post transplantation)
- risk of infection much higher with allogeneic than autologous transplantation due to myeloablative conditioning, neutropenia, immunsuppression to reduce graft vs host disease[1]
- bone marrow transplant nephropathy
- veno-occlusive disease of the liver, especially after chemotherapy with busulfan
- risk of secondary malignancy (allogeneic HSCT)
- skin: 27% 30-year cumulative incidence
- basal cell carcinoma 18.0%, squamous cell carcinoma 9.8%, melanoma 3.7%[14]
- buccal cavity
- central nervous system
- thyroid
- connective tissue
- skin: 27% 30-year cumulative incidence
- excess risk for adverse cardiovascular outcomes
- hazzard ratio ~ 2-3[2]
- excess risk of all-cause mortality
- hazzard ratio ~ 10[2]
* low incidence (< 10%
Management
- rapid hematologic & immunologic reconstitution is generally complete within 3-6 months
- allogeneic HSCT is treated for 6-12 months after transplantation with immunosuppressive agents to prevent allo-recognition of the patient by donor T-cells
- prescribe new medications with caution
- anti-rejection drug effects are wide
- drug interactions are common[1]
- immunizations prior to transplantation
- reimmunizations after HSCT
- antifungal prophylaxis
- fluconazole 6-12 mg/kg/day (max 400 mg/day) (IV or PO) from the start of conditioning until engraftment[8]
- echinocandin is an alternative to fluconazole[8]
- prophylaxis with fluconazole & a fluoroquinolone for neutropenic patients
- CMV prophylaxis
- monitoring cytomegalovirus DNA with pre-emptive therapy preferred to prophylaxis with ganciclovir[1]
- formerly, indicated for transplant recipients at risk for CMV
- ganciclovir, valganciclovir or high-dose acyclovir
- can reduce risk of lymphoproliferative disease
- Bactrim is used for prophylaxis against & treatment of Pneumocystis pneumonia
- treat complications
- BCNU-related interstitial pneumonitis is treated with glucocorticoids to prevent respiratory failure & death
- treatment of graft versus host disease (GVHD)
- complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity[13]
- lifelong surveillance for long-term complications
More general terms
More specific terms
Additional terms
- bone marrow transplant (BMT) nephropathy
- graft versus host disease (GVHD)
- vaccination after bone marrow transplantation
References
- ↑ Jump up to: 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018.
Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025 - ↑ Jump up to: 2.0 2.1 2.2 Chow EJ et al. Cardiovascular hospitalizations and mortality among recipients of hematopoietic stem cell transplantation. Ann Intern Med 2011 Jul 5; 155:21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21727290
- ↑ Wingard JR, Hsu J, Hiemenz JW. Hematopoietic stem cell transplantation: an overview of infection risks and epidemiology. Infect Dis Clin North Am. 2010 Jun;24(2):257-72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20466269
- ↑ Jump up to: 4.0 4.1 Asano-Mori Y. Fungal infections after hematopoietic stem cell transplantation. Int J Hematol. 2010 May;91(4):576-87 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20432074
- ↑ Nucci M, Anaissie E. Fungal infections in hematopoietic stem cell transplantation and solid-organ transplantation--focus on aspergillosis. Clin Chest Med. 2009 Jun;30(2):295-306, PMID: https://www.ncbi.nlm.nih.gov/pubmed/19375636
- ↑ Tomblyn M, Chiller T, Einsele H, Gress R et al Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009 Oct;15(10):1143-238 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19747629
- ↑ Jump up to: 7.0 7.1 Gadalla SM et al. Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia. JAMA 2015 Feb 10; 313:594. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25668263 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2108888
Saad A et al. Telomere length in hematopoietic stem cell transplantation for severe aplastic anemia. Is it ready for "prime time"? JAMA 2015 Feb 10; 313:571 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25668259 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2108869 - ↑ Jump up to: 8.0 8.1 8.2 Science M, Robinson PD, MacDonald T et al Guideline for primary antifungal prophylaxis for pediatric patients with cancer or hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2014 Mar;61(3):393-400 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24424789
- ↑ Majhail NS, Rizzo JD, Lee SJ et al Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012 Mar;18(3):348-71. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22178693 Free PMC Article
- ↑ Weigt SS, Gregson AL, Deng JC, Lynch JP 3rd, Belperio JA. Respiratory viral infections in hematopoietic stem cell and solid organ transplant recipients. Semin Respir Crit Care Med. 2011 Aug;32(4):471-93. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21858751 Free PMC Article
- ↑ Hashmi SK. Basics of Hematopoietic Cell Transplantation for Primary Care Physicians and Internists. Prim Care. 2016 Dec;43(4):693-701. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27866586
- ↑ Jump up to: 12.0 12.1 Kanter J, Liem RI, Bernaudin F et al. American Society of Hematology 2021 guidelines for sickle cell disease: Stem cell transplantation. Blood Adv 2021 Sep 28; 5:3668 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34581773 https://ashpublications.org/bloodadvances/article/5/18/3668/476988/American-Society-of-Hematology-2021-guidelines-for
- ↑ Jump up to: 13.0 13.1 Brooks M ASCO Releases Vaccination Guidelines for Adults With Cancer MDedge/Internal Medicine. March 28, 2024 https://www.mdedge.com/internalmedicine/article/268479/preventive-care/asco-releases-vaccination-guidelines-adults-cancer
- ↑ Jump up to: 14.0 14.1 Broman KK, Meng Q, Holmqvist A et al. Incidence of and Risk Factors for Cutaneous Malignant Neoplasms After Blood or Marrow Transplant. JAMA Dermatol. 2024. Dec 18. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39693095 https://jamanetwork.com/journals/jamadermatology/fullarticle/2827593
- ↑ Jump up to: 15.0 15.1 15.2 15.3 Astashchanka A, Ryan J, Lin E, et al. Pulmonary complications in hematopoietic stem cell transplant recipients - a clinician primer. J Clin Med. 2021;10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34362012
- ↑ National Heart, Lung, and Blood Institute (NHLBI) Blood and Bone Marrow Transplant https://www.nhlbi.nih.gov/health-topics/blood-and-bone-marrow-transplant