Contents

Search

bone marrow transplantation (BMT)

May be obsolete procedure since hematopoietic stem cells may be harvested from peripheral blood. Classification: Types of BMTs: 1) autologous a) stem cell harvesting from patient prior to high-dose chemotherapy &/or radiation b) cryopreservation c) reinfusion into the patient after chemotherapy to restore hematopoiesis 2) allogeneic a) HLA-matched donor b) HLA-identical sibling c) HLA-identical donor identified from the general population via searching international donor registries d) in some case, one antigen mismatch from a sibling may be tolerated e) allogeneic cells from fetal cord blood (rich in stem cells) may be associated with less graft-versus host disease Phases post BMT 1) pre-engraftment phase 1 (< 30 days post BMT) - profound neutropenia distinguishes BMT from other organ transplantation 2) post-engraftment phase 2 (30-100 days post BMT) 3) late phase 3 (> 100 days post BMT) Indications: 1) hematopoietic malignancies a) leukemia b) lymphoma c) myeloma 2) aplastic anemia 3) genetic blood disorders a) thalassemia b) sickle cell disease c) severe combined immunodeficiency 4) support for high-dose chemotherapy in which hematopoietic toxicity limits therapy (autologous BMT) a) breast cancer b) germ cell cancers c) ovarian cancer 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: 1) graft versus host disease (GVHD) (allogeneic BMT) a) acute GVHD generally occurs within 3 months of transplantation b) chronic GVHD may occur with taper of immunosuppression 2) opportunistic infections a) pancytopenic phase 1 (< 30 days post transplantation) 1] invasive pulmonary aspergillosis in neutropenic patients [1,4] 2] Herpes simplex virus 3] facultative gram negative bacilli 4] Staphylococcus epidermidis 5] gastrointestinal streptococci 6] Candida b) phase 2 (30-100 days post transplantation) 1] cytomegalovirus pneumonitis (allogeneic BMT) - generally occurs within 3 months of transplantation 2] Epstein-Barr virus* 3] Staphylococcus epidermidis 4] Candida 5] invasive pulmonary aspergillosis 6] Toxoplasma gondii* 7] Strongyloides stercoralis* 8] Pneumocystis jirovecii (late phase 2) c) phase 3, late complications (> 100 days post transplantation) 1] increased risk of infection with encapsulated organism - Streptococcus pneumoniae 2] cytomegalovirus pneumonitis 3] Varicella zoster reactivation (20-50%) a] dermatomal pain with vesicular rash b] disseminated vesicles with visceral involvement; liver, lung, brain 4] Epstein-Barr virus* 5] invasive pulmonary aspergillosis 6] Pneumocystis jirovecii 7] Toxoplasma gondii* 8] BCNU-related interstitial pneumonitis with autologous BMT d) respiratory & enteric viruses (all phases post transplantation) 3) bone marrow transplant nephropathy 4) veno-occlusive disease of the liver, especially after chemotherapy with busulfan 5) risk of secondary malignancy (allogeneic BMT) a) skin b) buccal cavity c) central nervous system d) thyroid e) connective tissue 6) excess risk for adverse cardiovascular outcomes - hazzard ratio ~ 2-3 [2] 7) excess risk of all-cause mortality - hazzard ratio ~ 10 [2] * low incidence (< 10% Management: 1) rapid hematologic & immunologic reconstitution is generally complete within 3-6 months 2) allogeneic BMT is treated for 6-12 months after trans- plantation with immunosuppressive agents to prevent allo- recognition of the patient by donor T-cells 3) prescribe new medications with caution a) anti-rejection drug effects are wide b) drug interactions are common [1] 4) immunizations prior to transplantation - see organ/tissue_transplantation 5) reimmunizations after BMT a) diptheria b) tetanus c) poliovirus (inactivated) d) Haemophilus influenzae B e) pertussis 6) prophylaxis with fluconozole & a fluoroquinolone for neutropenic patients 7) CMV prophylaxis a) indicated for transplant recipients at risk for CMV b) ganciclovir, valganciclovir or high-dose acyclovir c) can reduce risk of lymphoproliferative disease 8) Bactrim is used for prophylaxis against & treatment of Pneumocystis pneumonia 9) treat complications - BCNU-related interstitial pneumonitis is treated with glucocorticoids to prevent respiratory failure & death 10) treatment of graft versus host disease (GVHD) 11) lifelong surveillance for long-term complications

Related

bone marrow transplant (BMT) nephropathy graft versus host disease (GVHD) vaccination after bone marrow transplantation

General

hematopoietic stem cell transplantation (HSCT)

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 16. American College of Physicians, Philadelphia 1998, 2012
  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: 21727290
  3. 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: 20466269
  4. Asano-Mori Y. Fungal infections after hematopoietic stem cell transplantation. Int J Hematol. 2010 May;91(4):576-87 PMID: 20432074
  5. 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: 19375636
  6. 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: 19747629
  7. National Heart, Lung, and Blood Institute (NHLBI) Blood and Bone Marrow Transplant https://www.nhlbi.nih.gov/health-topics/blood-and-bone-marrow-transplant