stem cell transplantation
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Indications
- leukemias, lymphomas
- immunodeficiency syndrome
- aplastic anemia
- myelofibrosis
- myelodysplastic syndrome
- macular degeneration[11]
- multiple sclerosis[13]
Procedure
general
origin: sources of stem cells (see notes)
- cord blood
- 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
- bone marrow
- embryonic stem cells
specific disorders
- for leukemias/lymphoma
- induction & consolidation
- bone marrow biopsy when in remission
- if negative, consider stem cell transplantation
- use of reduced intensity conditioning regimens has diminished treatment-related morbidity & mortality & allowed older patients to undergo stem-cell transplantation[5]
- 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]
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
Complications
- graft vs host disease
- complications of immunosuppression
- also see Complications: section of organ transplantation
- febrile neutropenia
- relapse of leukemia/lymphoma
- delirium associated with long-term cognitive impairment, diminished quality of life[3]
- 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]
- fungal infection in the 1st few months even after recovery of neutropenia[5]
- long-term use of azithromycin after stem-cell transplantation for hematologic malignancy associated with increased risk of relapse & increased mortality[16]
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
- 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]
- mesangioblast stem cell show benefit in a dog model for Duschenne muscular dystrophy[2]
- gene therapy with retroviral vectors in combination with stem cell therapy corrects junctional epidermolysis bullosa[2]
- induced pluripotent stem cells injected into mdibrain of fetal rats improves symptoms in rat model of Parkinson's disease
- allogeneic peripheral-blood & bone-marrow stem cells result in equivalent survival for patients with high-risk hematologic malignancies[8]
- 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
- studies on intra-articular stem cell injections for ostearthritis of the knee are of poor quality[12]
Notes
- U.S. National Marrow Donor Program (NMDP)[11]
- 11 million donors & nearly 200,000 cord-blood units
More general terms
More specific terms
- cardiac Stem Cell Therapy
- intramuscular autologous bone marrow cell therapy
- stem cell transplantation in the elderly; geriatric stem cell transplantation
Additional terms
References
- ↑ 1.0 1.1 Schachinger V et al, Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006, 355:1210 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16990384
Lunde K et al, Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006, 355:1199 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16990383
Assmus B et al, Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006, 355:1222 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16990385
Schwartz RS, The politics and promise of stem-cell research. N Engl J Med 2006, 355:1189 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16990380
Rosenzweig A Cardiac cell therapy - Mixed results from mixed cells. N Engl J Med 2006, 355:1274 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16990391 - ↑ 2.0 2.1 2.2 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 - ↑ 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/17401011
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/18391196
- ↑ 5.0 5.1 5.2 5.3 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18 American College of Physicians, Philadelphia 2009, 2012, 2018.
- ↑ 6.0 6.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22084195 <Internet> http://jama.ama-assn.org/content/306/19/2110
Hare JM. Bone marrow therapy for myocardial infarction. JAMA 2011 Nov 14; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22084194 <Internet> http://jama.ama-assn.org/content/306/19/2110 - ↑ National Cancer Institute Blood-Forming Stem Cell Transplants https://www.cancer.gov/about-cancer/treatment/types/stem-cell-transplant/stem-cell-fact-sheet
- ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/23075175
Appelbaum FR. Pursuing the goal of a donor for everyone in need. N Engl J Med 2012 Oct 18; 367:1555. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23075182 - ↑ Ferraro F, Celso CL, Scadden D. Adult stem cels and their niches. Adv Exp Med Biol. 2010;695:155-68. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21222205
- ↑ 10.0 10.1 10.2 10.3 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25054717 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMsa1311707
- ↑ 11.0 11.1 11.2 11.3 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 - ↑ 12.0 12.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27655978 <Internet> http://jbjs.org/content/98/18/1511
- ↑ 13.0 13.1 13.2 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
- ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 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: https://www.ncbi.nlm.nih.gov/pubmed/28679741
- ↑ 15.0 15.1 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
- ↑ 16.0 16.1 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
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/27339055 Free PMC Article
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/24041869
- ↑ U.S. National Marrow Donor Program (NMDP) https://bethematchclinical.org
- ↑ Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers http://cis.nci.nih.gov/fact/7_41.htm