Tools
Hematopoietic Stem Cell Transplantation in Sickle Cell Disease
Introduction
Sickle cell disease (SCD) is the most common hemoglobinopathy in the United States. SCD affects about 100,000 Americans, mostly of African descent.[1] Approximately 20 million individuals worldwide are affected by SCD. The molecular basis of SCD was poorly understood when the disease was first described in the early 1900s. It was not until 1949 when Dr. Linus Pauling carried out a landmark study, that it was determined that this condition is caused by abnormal hemoglobin that sickles when exposed to a low-oxygen environment. The abnormal form of hemoglobin in SCD arises from a single amino acid mutation in the beta-globin gene called hemoglobin S.[2]
Because SCD is an autosomal recessive disorder, both beta-globin genes must be mutated for an individual to develop overt disease. When only a single copy of the gene is mutated, the resulting phenotype is termed sickle cell trait. Sickle cell trait is usually benign, but affected persons may develop sickled cells when exposed to exceptionally low pressures of oxygen.
Since 1949, scientists have made steady progress in understanding the complex molecular pathology of SCD. However, until about two decades ago, no known cure for this genetic disorder existed. According to Dr. Mary T. Basset, a physician during the American civil rights movement, SCD research, screening, and treatment received little to no funding and was neglected because patients were primarily of African descent.[3] One of the significant achievements of the civil rights movement in the 1970s was the establishment of the Sickle Cell Disease Association of America and the creation of the Sickle Cell Anemia Act of 1972. Since then, there has been greater public awareness of SCD and incrementally more funding towards finding a cure, culminating in the first bone marrow stem cell transplant for SCD.
The Sickle Cell Anemia Act also improved screening processes for SCD. Today, in most parts of the United States, sickle cell screening is performed before discharging neonates from the hospital. This screening allows for early medical intervention and reduces morbidity and mortality from SCD. Treatment of SCD has improved, incorporating penicillin prophylaxis for children younger than 5, hydroxyurea to boost fetal hemoglobin levels, prophylactic blood transfusions, and pain medications, including opioids. Unfortunately, most of these treatments are palliative, and patients continue to experience poor quality of life because of recurrent pain episodes, end-organ damage, and a reduced life expectancy, underscoring the importance of seeking a cure for this condition.
In September 2018, the National Heart, Lung, and Blood Institute (NHLBI) launched the Cure Sickle Cell Initiative. Under this initiative, efforts are being made to develop new genetic approaches to cure SCD.[4][5] Advancement in gene therapy techniques has shown promising results in preclinical and clinical trials, but formal approval by the United States Food and Drug Administration (FDA) is still awaited.[2][3][6][7]
Anatomy and Physiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Anatomy and Physiology
Sickle cell disease is a genetic disorder inherited in an autosomal recessive manner. The hallmark mutation of SCD affects the sixth amino acid in the hemoglobin beta-chain, replacing the normal glutamate residue with valine. This point mutation results in hemoglobin polymerization in a hypoxic environment leading to the deformation of red blood cells and occlusion of the microvasculature. The resulting organ ischemia produces multiple organ damage typical of sickle cell disease.[2]
Indications
Although hematopoietic stem cell transplantation (HSCT) remains the only available curative therapy for SCD, not all affected individuals are eligible for such therapy, primarily because of the significant toxicities associated with the procedure. HSCT is currently indicated in persons with severe SCD with complications including stroke, acute chest syndrome, recurrent pain crisis, nephropathy, retinopathy, osteonecrosis of multiple joints, and priapism.[6] The decision to proceed with HSCT is complex and must include a discussion of potential benefits and risks, such as infection, graft-versus-host disease (GVHD), and organ injury from the conditioning regimen. In addition, HSCT can have unpredictable effects on preexisting heart, lung, and kidney diseases. Transplantation is only indicated when the benefits outweigh these risks.[8][9][10]
HSCT should ideally be performed in children with SCD at high risk for severe disease before the onset of complications. Unfortunately, without effective and validated biomarkers, predicting when such individuals might develop complications is challenging. The development of effective medical therapies has also complicated decisions regarding HSCT, as there are no prospective head-to-head comparisons of these medical therapies against HSCT. Thus, HSCT is more likely to benefit individuals who do not wish to utilize chronic medical therapy. The uncertainty around HSCT in SCD is reflected in the 2014 guidelines issued by the NHLBI, acknowledging that additional research was required for patient and donor selection and to determine the optimal transplantation regimen before HSCT could be made widely available as a curative procedure for SCD.[11]
It is generally agreed that HSCT is indicated in children with progressive organ dysfunction, such as worsening cardiac, renal, and pulmonary function, recurrent stroke, and recurrent priapism, despite the institution of optimal medical therapy. HSCT can also be considered in older adolescents and young adults who can make an informed decision regarding the risks and benefits of the procedure. Regardless of the patient's age, the availability of a suitable donor, such as a fully matched sibling, is an essential requirement.[12] Alternate donors, such as haploidentical and matched unrelated donors, may be considered in selected cases.[13]
The optimal age for receiving HSCT has not been established. However, several retrospective studies have shown improved survival after HSCT in children compared to adults, especially in children below the age of 10.[14][15] Similarly, the optimal source of donor stem cells is unclear. Donor stem cells can be derived from umbilical cord blood, bone marrow, or mobilized peripheral blood. Of these sources, umbilical cord blood and bone marrow are expected to have the best outcomes; stem cells from these sites are associated with a lower risk of GVHD than peripheral blood. However, at least one study of HSCT in SCD did not show a lower incidence of GVHD with cord blood and bone marrow stem cells, although overall survival was superior with these sources compared to peripheral blood stem cells.[15]
Preparation
Hematopoietic stem cell transplantation is a complicated process involving multiple tests and extensive preparation. Routine laboratory testing must be performed, including a complete blood count, comprehensive metabolic profile, and 24-hour urine protein and creatinine. Brain magnetic resonance imaging and magnetic resonance angiography (MRI/MRA) is necessary to determine the extent of brain infarcts and vascular abnormalities. An echocardiogram must be performed to estimate pulmonary arterial pressures. Dental clearance and pulmonary function tests are also a part of pretransplant testing.
Most importantly, HLA-typing must be performed to identify a suitable donor. The red cell phenotype of the recipient and donor is obtained. Screening for donor-directed antibodies is undertaken because of the risk of pure red cell aplasia after HSCT.[16][17] Hydroxyurea must be discontinued before HSCT, and exchange transfusion is often initiated to minimize the risk of complications. Patients and their families should be counseled about the risk of infertility; options for fertility preservation should be offered before initiating the transplantation process.
Technique or Treatment
Bone marrow transplantation is more accurately described as hematopoietic stem cell transplantation (HSCT). HSCT is broadly categorized into two types, autologous, where an individual receives their own stem cells, and allogeneic, where an individual receives stem cells from another individual, termed the donor. Autologous HSCT is typically not helpful in SCD unless the stem cells have been modified by genetic techniques to correct the underlying genetic mutation. Allogeneic HSCT is more widely used; the donor must be matched and can be a sibling or unrelated donor, although matched sibling donors are preferred. Matching refers to human leukocyte antigen (HLA); donors and recipients are considered fully matched if they have identical sequences at 8 out of 8 HLA loci.
Hematopoietic stem cell transplantation techniques have been developed and refined continuously since the first transplant was performed in 1984. The HSCT technique requires a conditioning or preparative regimen of chemotherapy to ablate the stem cells of the recipient. The aplastic marrow is repopulated by healthy donor stem cells. The preparative regimen of the first HSCT in 1984 included cyclophosphamide at 120 mg/kg and fractionated total body irradiation.[18] The patient then received GVHD prophylaxis consisting of a short course of methotrexate and methylprednisolone. Since then, significant strides have been made with conditioning regimens, including developing lower-intensity treatments such as nonmyeloablative and reduced-intensity conditioning regimens that induce cytopenias to allow donor cell engraftment but do not completely ablate the marrow.[19] Administration of cyclophosphamide after HSCT is another advancement that has markedly improved outcomes in allogeneic HSCT, but its use is typically limited to patients receiving haploidentical stem cells.[20][21]
Myeloablative regimens that combine cytotoxic chemotherapy and total body irradiation are typically used for HSCT in SCD. Examples of commonly employed regimens include busulfan plus cyclophosphamide or busulfan plus fludarabine. One study described the combination of thiotepa, fludarabine, and treosulfan with excellent long-term results.[22] Once the conditioning regimen has been administered and the donor stem cells have been transfused, the patient is assessed for engraftment and donor chimerism, the proportion of hematopoietic cells derived from the donor. Donor chimerism of ≥20% is needed to assure the production of enough non-HbS hemoglobin that sickling will not occur, thus producing a clinical cure.[12] Care should be taken to avoid using granulocyte-colony stimulating factor after transplantation because of reports of fatal cases of sickle cell crises with this agent.[23] Recipients should receive immunizations after the transplant procedure per standard protocols for bone marrow transplantation. Prophylaxis against GVHD and opportunistic infections must be initiated similarly to other indications for HSCT.
Complications
Since the first HSCT was performed in 1984, over 1200 cases have been described. Complications arising from transplantation can be grouped into medical complications from the conditioning regimen, the transplantation itself, the immunosuppressive therapy used after transplantation, or financial toxicity.
Conditioning regimens are highly toxic and can be associated with short-term organ injury and long-term effects such as infertility and secondary malignancies.[24][25] Transplantation itself is associated with a high risk of morbidity and mortality, especially if there is a mismatch. HSCT is safest when a matched donor is available, but unfortunately, only a few transplant candidates have such donors. Even with a suitable donor, there is still a 9% risk of graft rejection and a 15% risk of chronic GVHD.[15] The immunosuppressive therapy needed to suppress GVHD predisposes patients to opportunistic infections, which can occasionally be fatal. Nonhealing leg wounds in some patients compound the risk of infection, although this is not necessarily a barrier to HSCT.[26] Finally, significant financial costs associated with HSCT can be burdensome, especially for patients from socioeconomically disadvantaged backgrounds.[27]
The potential for one or more of these complications should be carefully considered when evaluating an individual with SCD for HSCT. The patient and their caregivers should be educated about these complications to make an informed decision. Moreover, with appropriate counseling, the patient and their caregivers are better prepared to deal with complications, ultimately improving outcomes. Mitigation strategies for these complications vary depending on the circumstances.
Complications in the immediate period during and after transplantation, such as infections, organ injury from the conditioning regimen, and acute GVHD, are usually managed by the transplant team with protocols similar to those used in patients receiving HSCT for other indications. However, more long-term complications, such as late secondary malignancies, are often managed with close screening, the burden of which is shared between the transplant team and other health professionals. Infertility should be managed preemptively with counseling regarding fertility preservation options before the transplantation procedure.
Clinical Significance
HSCT currently represents the only curative option for SCD, which is otherwise a chronic and incurable condition with complications that affect multiple organs leading to reduced quality of life and shortened survival. HSCT is associated with excellent overall and event-free survival and improvement in vaso-occlusive phenomena.[28] However, HSCT does carry a risk of significant toxicity, which limits its use in clinical practice to young patients with good organ function but at high risk of complications. This represents only a small portion of the population living with SCD.
Allogeneic HSCT also requires the identification of a suitable donor, typically a matched sibling. Thus allogeneic HSCT is not an option for most patients with SCD, despite the advances that have been made in this field. Autologous stem cell transplantation with genetically modified stem cells is expected to overcome some of these limitations. Although not commercially available, several gene therapy treatments are awaiting FDA approval.[7]
Enhancing Healthcare Team Outcomes
Sickle cell disease is a complex disorder affecting multiple organ systems that requires care coordination among various teams of healthcare professionals to ensure optimal outcomes. HSCT is a highly specialized field requiring a team of trained physicians, nurses, pharmacists, stem cell technicians, and other services such as infectious disease and intensive care teams. Close coordination among these teams is critical for successful outcomes; HSCT procedures are only performed at tertiary care centers with adequate experience and infrastructure.
However, optimizing these outcomes requires extending this effort beyond the transplant center to pediatric and adult hematologists working in the community so that affected individuals are referred at the appropriate time for evaluation for HSCT. Creating awareness of this therapeutic option among hematologists caring for individuals living with SCD is critical. Expanding access to HSCT and continuing research into improving the safety and efficacy of HSCT in patients with SCD represent the measures most likely to improve patient safety and outcomes.
References
Kavanagh PL, Fasipe TA, Wun T. Sickle Cell Disease: A Review. JAMA. 2022 Jul 5:328(1):57-68. doi: 10.1001/jama.2022.10233. Epub [PubMed PMID: 35788790]
Zivot A, Lipton JM, Narla A, Blanc L. Erythropoiesis: insights into pathophysiology and treatments in 2017. Molecular medicine (Cambridge, Mass.). 2018 Mar 23:24(1):11. doi: 10.1186/s10020-018-0011-z. Epub 2018 Mar 23 [PubMed PMID: 30134792]
Bernaudin F, Verlhac S, Peffault de Latour R, Dalle JH, Brousse V, Petras E, Thuret I, Paillard C, Neven B, Galambrun C, Divialle-Doumdo L, Pondarré C, Guitton C, Missud F, Runel C, Jubert C, Elana G, Ducros-Miralles E, Drain E, Taïeb O, Arnaud C, Kamdem A, Malric A, Elmaleh-Bergès M, Vasile M, Leveillé E, Socié G, Chevret S, DREPAGREFFE Trial Investigators. Association of Matched Sibling Donor Hematopoietic Stem Cell Transplantation With Transcranial Doppler Velocities in Children With Sickle Cell Anemia. JAMA. 2019 Jan 22:321(3):266-276. doi: 10.1001/jama.2018.20059. Epub [PubMed PMID: 30667500]
Urbinati F, Wherley J, Geiger S, Fernandez BC, Kaufman ML, Cooper A, Romero Z, Marchioni F, Reeves L, Read E, Nowicki B, Grassman E, Viswanathan S, Wang X, Hollis RP, Kohn DB. Preclinical studies for a phase 1 clinical trial of autologous hematopoietic stem cell gene therapy for sickle cell disease. Cytotherapy. 2017 Sep:19(9):1096-1112. doi: 10.1016/j.jcyt.2017.06.002. Epub 2017 Jul 18 [PubMed PMID: 28733131]
Level 1 (high-level) evidenceUchida N, Fujita A, Hsieh MM, Bonifacino AC, Krouse AE, Metzger ME, Donahue RE, Tisdale JF. Bone Marrow as a Hematopoietic Stem Cell Source for Gene Therapy in Sickle Cell Disease: Evidence from Rhesus and SCD Patients. Human gene therapy. Clinical development. 2017 Sep:28(3):136-144. doi: 10.1089/humc.2017.029. Epub 2017 Apr 17 [PubMed PMID: 28447889]
Krishnamurti L, Neuberg DS, Sullivan KM, Kamani NR, Abraham A, Campigotto F, Zhang W, Dahdoul T, De Castro L, Parikh S, Bakshi N, Haight A, Hassell KL, Loving R, Rosenthal J, Smith SL, Smith W, Spearman M, Stevenson K, Wu CJ, Wiedl C, Waller EK, Walters MC. Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. American journal of hematology. 2019 Apr:94(4):446-454. doi: 10.1002/ajh.25401. Epub 2019 Feb 11 [PubMed PMID: 30637784]
Level 3 (low-level) evidenceKingwell K. First CRISPR therapy seeks landmark approval. Nature reviews. Drug discovery. 2023 May:22(5):339-341. doi: 10.1038/d41573-023-00050-8. Epub [PubMed PMID: 37012339]
Alonso L, González-Vicent M, Belendez C, Badell I, Sastre A, Rodríguez-Villa A, Bermúdez-Cortés M, Hladun R, Díaz de Heredia C. Hematopoietic stem cell transplantation in pediatric patients with thalassemia and sickle cell disease: An experience of the Spanish Working Group for Bone Marrow Transplantation in Children (GETMON). Medicina clinica. 2019 Feb 15:152(4):135-140. doi: 10.1016/j.medcli.2018.05.013. Epub 2018 Jul 9 [PubMed PMID: 30001893]
Brennan-Cook J, Bonnabeau E, Aponte R, Augustin C, Tanabe P. Barriers to Care for Persons With Sickle Cell Disease: The Case Manager's Opportunity to Improve Patient Outcomes. Professional case management. 2018 Jul/Aug:23(4):213-219. doi: 10.1097/NCM.0000000000000260. Epub [PubMed PMID: 29846351]
Level 3 (low-level) evidenceWalters MC. Update of hematopoietic cell transplantation for sickle cell disease. Current opinion in hematology. 2015 May:22(3):227-33. doi: 10.1097/MOH.0000000000000136. Epub [PubMed PMID: 25767957]
Level 3 (low-level) evidenceYawn BP,Buchanan GR,Afenyi-Annan AN,Ballas SK,Hassell KL,James AH,Jordan L,Lanzkron SM,Lottenberg R,Savage WJ,Tanabe PJ,Ware RE,Murad MH,Goldsmith JC,Ortiz E,Fulwood R,Horton A,John-Sowah J, Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10 [PubMed PMID: 25203083]
Guilcher GMT, Truong TH, Saraf SL, Joseph JJ, Rondelli D, Hsieh MM. Curative therapies: Allogeneic hematopoietic cell transplantation from matched related donors using myeloablative, reduced intensity, and nonmyeloablative conditioning in sickle cell disease. Seminars in hematology. 2018 Apr:55(2):87-93. doi: 10.1053/j.seminhematol.2018.04.011. Epub 2018 Apr 25 [PubMed PMID: 29958564]
Hulbert ML, Shenoy S. Hematopoietic stem cell transplantation for sickle cell disease: Progress and challenges. Pediatric blood & cancer. 2018 Sep:65(9):e27263. doi: 10.1002/pbc.27263. Epub 2018 May 24 [PubMed PMID: 29797658]
Arnold SD, Brazauskas R, He N, Li Y, Aplenc R, Jin Z, Hall M, Atsuta Y, Dalal J, Hahn T, Khera N, Bonfim C, Majhail NS, Diaz MA, Freytes CO, Wood WA, Savani BN, Kamble RT, Parsons S, Ahmed I, Sullivan K, Beattie S, Dandoy C, Munker R, Marino S, Bitan M, Abdel-Azim H, Aljurf M, Olsson RF, Joshi S, Buchbinder D, Eckrich MJ, Hashmi S, Lazarus H, Marks DI, Steinberg A, Saad A, Gergis U, Krishnamurti L, Abraham A, Rangarajan HG, Walters M, Lipscomb J, Saber W, Satwani P. Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases. Haematologica. 2017 Nov:102(11):1823-1832. doi: 10.3324/haematol.2017.169581. Epub 2017 Aug 17 [PubMed PMID: 28818869]
Gluckman E, Cappelli B, Bernaudin F, Labopin M, Volt F, Carreras J, Pinto Simões B, Ferster A, Dupont S, de la Fuente J, Dalle JH, Zecca M, Walters MC, Krishnamurti L, Bhatia M, Leung K, Yanik G, Kurtzberg J, Dhedin N, Kuentz M, Michel G, Apperley J, Lutz P, Neven B, Bertrand Y, Vannier JP, Ayas M, Cavazzana M, Matthes-Martin S, Rocha V, Elayoubi H, Kenzey C, Bader P, Locatelli F, Ruggeri A, Eapen M, Eurocord, the Pediatric Working Party of the European Society for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research. Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood. 2017 Mar 16:129(11):1548-1556. doi: 10.1182/blood-2016-10-745711. Epub 2016 Dec 13 [PubMed PMID: 27965196]
Level 3 (low-level) evidenceKato GJ, Piel FB, Reid CD, Gaston MH, Ohene-Frempong K, Krishnamurti L, Smith WR, Panepinto JA, Weatherall DJ, Costa FF, Vichinsky EP. Sickle cell disease. Nature reviews. Disease primers. 2018 Mar 15:4():18010. doi: 10.1038/nrdp.2018.10. Epub 2018 Mar 15 [PubMed PMID: 29542687]
Frangoul H, Evans M, Isbell J, Bruce K, Domm J. Haploidentical hematopoietic stem cell transplant for patients with sickle cell disease using thiotepa, fludarabine, thymoglobulin, low dose cyclophosphamide, 200 cGy tbi and post transplant cyclophosphamide. Bone marrow transplantation. 2018 May:53(5):647-650. doi: 10.1038/s41409-017-0077-1. Epub 2018 Jan 16 [PubMed PMID: 29339800]
Fitzhugh CD, Abraham AA, Tisdale JF, Hsieh MM. Hematopoietic stem cell transplantation for patients with sickle cell disease: progress and future directions. Hematology/oncology clinics of North America. 2014 Dec:28(6):1171-85. doi: 10.1016/j.hoc.2014.08.014. Epub 2014 Sep 29 [PubMed PMID: 25459186]
Level 3 (low-level) evidenceBernaudin F, Pondarré C, Galambrun C, Thuret I. Allogeneic/Matched Related Transplantation for β-Thalassemia and Sickle Cell Anemia. Advances in experimental medicine and biology. 2017:1013():89-122. doi: 10.1007/978-1-4939-7299-9_4. Epub [PubMed PMID: 29127678]
Level 3 (low-level) evidenceRangarajan HG, Abu-Arja R, Pai V, Guilcher GMT, Soni S. Outcomes of Unrelated Donor Stem Cell Transplantion with Post-Transplant Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients with Severe Sickle Cell Disease. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018 Feb:24(2):413-417. doi: 10.1016/j.bbmt.2017.10.030. Epub 2017 Oct 20 [PubMed PMID: 29061531]
Fitzhugh CD, Hsieh MM, Taylor T, Coles W, Roskom K, Wilson D, Wright E, Jeffries N, Gamper CJ, Powell J, Luznik L, Tisdale JF. Cyclophosphamide improves engraftment in patients with SCD and severe organ damage who undergo haploidentical PBSCT. Blood advances. 2017 Apr 25:1(11):652-661. doi: 10.1182/bloodadvances.2016002972. Epub 2017 Apr 19 [PubMed PMID: 29296707]
Level 3 (low-level) evidenceStrocchio L, Zecca M, Comoli P, Mina T, Giorgiani G, Giraldi E, Vinti L, Merli P, Regazzi M, Locatelli F. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease. British journal of haematology. 2015 Jun:169(5):726-36. doi: 10.1111/bjh.13352. Epub 2015 Mar 27 [PubMed PMID: 25818248]
Adler BK, Salzman DE, Carabasi MH, Vaughan WP, Reddy VV, Prchal JT. Fatal sickle cell crisis after granulocyte colony-stimulating factor administration. Blood. 2001 May 15:97(10):3313-4 [PubMed PMID: 11368061]
Level 3 (low-level) evidenceNickel RS, Maher JY, Hsieh MH, Davis MF, Hsieh MM, Pecker LH. Fertility after Curative Therapy for Sickle Cell Disease: A Comprehensive Review to Guide Care. Journal of clinical medicine. 2022 Apr 21:11(9):. doi: 10.3390/jcm11092318. Epub 2022 Apr 21 [PubMed PMID: 35566443]
Eapen M, Brazauskas R, Williams DA, Walters MC, St Martin A, Jacobs BL, Antin JH, Bona K, Chaudhury S, Coleman-Cowger VH, DiFronzo NL, Esrick EB, Field JJ, Fitzhugh CD, Kanter J, Kapoor N, Kohn DB, Krishnamurti L, London WB, Pulsipher MA, Talib S, Thompson AA, Waller EK, Wun T, Horowitz MM. Secondary Neoplasms After Hematopoietic Cell Transplant for Sickle Cell Disease. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Apr 20:41(12):2227-2237. doi: 10.1200/JCO.22.01203. Epub 2023 Jan 9 [PubMed PMID: 36623245]
Connor JL Jr, Minniti CP, Tisdale JF, Hsieh MM. Sickle Cell Anemia and Comorbid Leg Ulcer Treated With Curative Peripheral Blood Stem Cell Transplantation. The international journal of lower extremity wounds. 2017 Mar:16(1):56-59. doi: 10.1177/1534734616685636. Epub 2017 Jan 9 [PubMed PMID: 28682672]
Krishnamurti L. Gaps in Medicaid Coverage and Financial Toxicity: A Health Disparity in Hematopoietic Cell Transplantation for Sickle Cell Disease. Transplantation and cellular therapy. 2021 Apr:27(4):284-285. doi: 10.1016/j.jtct.2021.03.016. Epub [PubMed PMID: 33836866]
Walters MC, Hardy K, Edwards S, Adamkiewicz T, Barkovich J, Bernaudin F, Buchanan GR, Bunin N, Dickerhoff R, Giller R, Haut PR, Horan J, Hsu LL, Kamani N, Levine JE, Margolis D, Ohene-Frempong K, Patience M, Redding-Lallinger R, Roberts IA, Rogers ZR, Sanders JE, Scott JP, Sullivan KM, Multicenter Study of Bone Marrow Transplantation for Sickle Cell Disease. Pulmonary, gonadal, and central nervous system status after bone marrow transplantation for sickle cell disease. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2010 Feb:16(2):263-72. doi: 10.1016/j.bbmt.2009.10.005. Epub 2009 Oct 12 [PubMed PMID: 19822218]
Level 2 (mid-level) evidence