Contents

Search

stem cell transplantation

Indications: 1) leukemias, lymphomas 2) immunodeficiency syndrome 3) aplastic anemia 4) myelofibrosis 5) myelodysplastic syndrome 6) macular degeneration [11] 7) multiple sclerosis [13] Procedure: general 1) premedicate with Benadryl & Tylenol 2) 2-5 x 10E6 cells transfused origin: sources of stem cells (see notes) 1) cord blood - unrelated-matched (6/6 HLA loci) or minimally mismatched (5/6 loci) donor [10] - single-cord units often lack an adequate cell dose for transplantation in patients > years of age [10] 2) peripheral blood - faster recovery than bone marrow transplantation - HLA-matched related donor. - unrelated-matched (8/8 HLA loci) or minimally mismatched (7/8 loci) donor [10] - HLA-haploidentical related donor [15] - similar outcomes to HLA-matched related donor - greatly expands pool of available donors 3) bone marrow 4) embryonic stem cells specific disorders 1) for leukemias/lymphoma a) induction & consolidation b) bone marrow biopsy when in remission -> if negative, consider stem cell transplantation c) use of reduced intensity conditioning regimens has diminished treatment-related morbidity & mortality & allowed older patients to undergo stem-cell transplantation [5] d) immunosuppression is required to facilitate engraftment & inhibit graft-vs-host disease in allogeneic stem-cell transplantation - postengraftment: taper immunosuppession conditioning regimens - high-intensity: busulfan or total body irradiation - low-intensity: cyclophosphamide +/- antithymocyte globulin or fludarabine phosphate [13] Complications: 1) graft vs host disease 2) complications of immunosuppression - also see Complications: section of organ transplantation - febrile neutropenia 3) relapse of leukemia/lymphoma 4) delirium associated with long-term cognitive impairment, diminished quality of life [3] 5) major bleeding including intracranial hemorrhage associated with thrombocytopenia [14] - bleeding with allogeneic transplants greater than with autologous transplants (21% vs 10%) or after chemotherapy (10%) [14] - bleeding risk greater for platelet counts < 5000/uL than > 80,000/uL, but no clear pattern of decreasing risk with increasing platelet counts [14] - patients with autologous stem cell transplantation at risk only with platelet count < 5000/uL [14] - bleeding risk greater if hematocrit < 25 (RR=1.3), aPTT > 30 (RR=1.4) or > 50 (RR=2.3), INR > 1.2 (RR=1.5) or > 1.5 (RR=2.0) [14] - RBC transfusion or platelet transfusion not associated with diminished next day bleeding [14] 6) fungal infection in the 1st few months even after recovery of neutropenia [5] 7) long-term use of azithromycin after stem-cell transplantation for hematologic malignancy associated with increased risk of relapse & increased mortality [16] 8) allogeneic stem-cell transplantation is not associated with an increased risk malignant mutations [19] Management: - prophylaxis with for Pneumocystis jirovecii with TMP-SMX - prophylaxis for fungal infection with posaconazole for 1st few months after allogeneic stem cell transplantation [5] Clinical trials: 1) 2 of 3 studies found small benefit in intracoronary infusion of bone marrow-derived stem cells within 7 days of myocardial infarction (MI); benefit noted 3 months after MI [1]; when infusion of stem cells is delayed 2-3 weeks, no benefit in left ventricular function is found [6] 2) mesangioblast stem cell show benefit in a dog model for Duschenne muscular dystrophy [2] 3) gene therapy with retroviral vectors in combination with stem cell therapy corrects junctional epidermolysis bullosa [2] 4) induced pluripotent stem cells injected into mdibrain of fetal rats improves symptoms in rat model of Parkinson's disease 5) allogeneic peripheral-blood & bone-marrow stem cells result in equivalent survival for patients with high-risk hematologic malignancies [8] 6) transplantation with retinal pigment epithelium derived from human embryonic stem cells (macular degeneration) [11] - > 50% with improvements in visual acuity - at 22 months, stem cells well tolerated 7) studies on intra-articular stem cell injections for ostearthritis of the knee are of poor quality [12] Mechanism of action: - stem cells reconstitute ablated cell lines - in allogeneic stem-cell transplantation for AML, graft-versus-leukemia (GVL) effect, mediated via donor T cells & NK cells, eliminates residual host acute myeloid leukemia (AML) cells Notes: - U.S. National Marrow Donor Program (NMDP) [11] - 11 million donors & nearly 200,000 cord-blood units

Related

stem cell

Specific

cardiac Stem Cell Therapy intramuscular autologous bone marrow cell therapy stem cell transplantation in the elderly; geriatric stem cell transplantation

General

cell transplantation

References

  1. Schachinger V et al, Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006, 355:1210 PMID: 16990384 - Lunde K et al, Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006, 355:1199 PMID: 16990383 - Assmus B et al, Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006, 355:1222 PMID: 16990385 - Schwartz RS, The politics and promise of stem-cell research. N Engl J Med 2006, 355:1189 PMID: 16990380 - Rosenzweig A Cardiac cell therapy - Mixed results from mixed cells. N Engl J Med 2006, 355:1274 PMID: 16990391
  2. Sampaolesi M et al, Mesangioblast stem cells ameliorate muscle dysfunction in dystrophic dogs. Nature 2006, 444:574 - Mavillo F et al, Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 2006, 12:1397
  3. Fann JR et al, Impact of delirium on cognition, distress, and health-related quality of life after hematopoietic stem-cell transplantation. J Clin Oncol 2007, 25:1223 PMID: 17401011
  4. Wernig M et al, Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci USA 2008, 105:5856 PMID: 18391196
  5. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18 American College of Physicians, Philadelphia 2009, 2012, 2018.
  6. Traverse JH et al. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial. JAMA 2011 Nov 14 PMID: 22084195 http://jama.ama-assn.org/content/306/19/2110 - Hare JM. Bone marrow therapy for myocardial infarction. JAMA 2011 Nov 14; PMID: 22084194 http://jama.ama-assn.org/content/306/19/2110
  7. National Cancer Institute Blood-Forming Stem Cell Transplants https://www.cancer.gov/about-cancer/treatment/types/stem-cell-transplant/stem-cell-fact-sheet
  8. Journal Watch Oncology and Hematology October 17, 2012 Massachusetts Medical Society http://www.jwatch.org - Anasetti C et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med 2012 Oct 18; 367:1487. PMID: 23075175 - Appelbaum FR. Pursuing the goal of a donor for everyone in need. N Engl J Med 2012 Oct 18; 367:1555. PMID: 23075182
  9. Ferraro F, Celso CL, Scadden D. Adult stem cels and their niches. Adv Exp Med Biol. 2010;695:155-68. PMID: 21222205
  10. Gragert L et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med 2014 Jul 24; 371:339. PMID: 25054717 http://www.nejm.org/doi/full/10.1056/NEJMsa1311707
  11. Orciari Herman A, Fairchild DG, Di Francesco L "First Evidence" of Long-Term Safety and Tolerability of Human Embryonic Stem Cell Treatment. Physician's First Watch, Oct 15, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Schwartz SD et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: Follow-up of two open-label phase 1/2 studies. Lancet 2014 Oct 15 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961376-3/fulltext
  12. Chahla J, Piuzzi NS, Mitchell JJ et al. Intra-articular cellular therapy for osteoarthritis and focal cartilage defects of the knee: A systematic review of the literature and study quality analysis. J Bone Joint Surg Am 2016 Sep 21 PMID: 27655978 http://jbjs.org/content/98/18/1511
  13. Muraro PA, Pasquini M, Atkins HL et al Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurol. Published online February 20, 2017 http://jamanetwork.com/journals/jamaneurology/fullarticle/2604135
  14. Uhl L, Assmann SF, Hamza TH et al. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood 2017 Sep 7; 130:1247 PMID: 28679741
  15. O'Neil A Haploidentical HSCTs Suffice When HLA-Identical Siblings Not Available. Expands donor pool for patients with AML, myeloma, and other heme malignancies. MedPage Today. ASCO Reading Room. Feb 7, 2018 https://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/70997
  16. Walker M FDA Warns Against Long-Term Zmax Use in Certain Cancer Patients. Heightened risk of relapse, death seen in study of stem cell transplant recipients. MedPage Today. August 03, 2018 https://www.medpagetoday.com/hematologyoncology/hematology/74403
  17. Ullmann AJ, Schmidt-Hieber M, Bertz H et al Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol. 2016 Sep;95(9):1435-55. PMID: 27339055 Free PMC Article
  18. Ariza-Heredia EJ, Nesher L, Chemaly RF. Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett. 2014 Jan 1;342(1):1-8. Review. PMID: 24041869
  19. Mallapaty S Do stem-cell transplants increase cancer risk? Long-lived recipients offer clues. Nature. 2024 Oct 25. PMID: 39455826 https://www.nature.com/articles/d41586-024-03450-x
  20. U.S. National Marrow Donor Program (NMDP) https://bethematchclinical.org
  21. Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers http://cis.nci.nih.gov/fact/7_41.htm