Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease

Bernaudin, Françoise; Socié, Gérard; Kuentz, Mathieu; Chevret, Sylvie; Duval, Michel; Bertrand, Yves; Vannier, Jean‐Pierre; Yakouben, Karima; Thuret, Isabelle; Bordigoni, Pierre; Fischer, Alain; Lutz, Patrick; Stéphan, Jean-Louis; Dhédin, Nathalie; Plouvier, Emmanuel; Margueritte, Geneviève; Bories, Dominique; Verlhac, Suzanne; Esperou, Hélène; Coïc, Léna; Vernant, Jean‐Paul; Gluckman, Éliane

doi:10.1182/blood-2007-03-079665

Cited by 449 publications

(483 citation statements)

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“…A multicenter trial showed that 7 out of 16 patients with seizures had posterior leukoencephalopathy secondary to CSP toxicity suggesting that an alternative medication for GVHD prophylaxis should be considered. 9 Walters et al 7 have shown in a multicenter trial that of 10 engrafted patients with prior stroke, all had stable or improved MRI scan. All our five patients that had follow-up MRI/MRA showed stable disease with no worsening or improvement.…”

Section: Discussionmentioning

confidence: 98%

“…[7][8][9] Seizure secondary to CSP with MRI changes suggestive of posterior leukoencephalopathy was commonly seen in our patients even with the use of anticonvulsant prophylaxis. A multicenter trial showed that 7 out of 16 patients with seizures had posterior leukoencephalopathy secondary to CSP toxicity suggesting that an alternative medication for GVHD prophylaxis should be considered.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9] Important indications include stroke, history of recurrent hospitalizations or exchange transfusion for acute chest syndrome, and recurrent vaso-occlusive pain crisis (X 3 episodes per year).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience

Majumdar

Robertson

Robinson

et al. 2009

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience

Majumdar

Robertson

Robinson

et al. 2009

Bone Marrow Transplant

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“…The event-free survival and overall survival reported in this updated study of adults, aged 16 through 65 years, are comparable with those of matched sibling transplants in children with sickle cell disease, aged 2 through 22 years, receiving myeloablative conditioning regimens. [13][14][15] Importantly, both acute (0%) and chronic graft-vs-host disease (0%) were significantly lower than the rates reported for children (12.5%-40% and 40%, respectively). In addition, both morbidity and treatment-related mortality appear significantly less than those previously reported about children receiving matched-sibling transplants despite significantly greater fixed organ dysfunction and alloimmunization in these adult transplant recipients.…”

Section: Reconsideration Of Age As a Contraindication For Curative Thmentioning

confidence: 86%

“…However, this cohort does represent an older group of patients with sickle cell disease who have significant premorbid conditions, and the patients tolerated the preparative regimen with engraftment rates similar to myeloablative regimens, even among children with sickle cell disease. [13][14][15] A subset of patients had donor CD3 chimerism of less than 50%, and these adults continued to take immunosuppression medications. When comparing the pretransplant medical regimen with posttransplant, these patients should still be experiencing a more positive experience.…”

Section: Reconsideration Of Age As a Contraindication For Curative Thmentioning

confidence: 99%

Reconsideration of Age as a Contraindication for Curative Therapy of Sickle Cell Disease

King

DiPersio

2014

JAMA

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Nonmyeloablative HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Phenotype

Hsieh

Fitzhugh

Weitzel

et al. 2014

JAMA

299

338

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IMPORTANCE Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but toxicity may be prohibitive for adults. Nonmyeloablative transplantation has been attempted with degrees of preparative regimen intensity, but graft rejection and graft-vs-host disease remain significant. OBJECTIVE To determine the efficacy, safety, and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia. DESIGN, SETTING, AND PARTICIPANTS From July 16, 2004, to October 25, 2013, 30 patients aged 16–65 years with severe disease enrolled in this nonmyeloablative transplant study, consisting of alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells (5.5–31.7 × 106 cells/kg) from human leukocyte antigen–matched siblings. MAIN OUTCOMES AND MEASURES The primary end point was treatment success at 1 year after the transplant, defined as a full donor-type hemoglobin for patients with sickle cell disease and transfusion independence for patients with thalassemia. The secondary end points were the level of donor leukocyte chimerism; incidence of acute and chronic graft-vs-host disease; and sickle cell–thalassemia disease-free survival, immunologic recovery, and changes in organ function, assessed by annual brain imaging, pulmonary function, echocardiographic image, and laboratory testing. RESULTS Twenty-nine patients survived a median 3.4 years (range, 1–8.6), with no nonrelapse mortality. One patient died from intracranial bleeding after relapse. As of October 25, 2013, 26 patients (87%) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. The mean donor T-cell level was 48% (95% CI, 34%–62%); the myeloid chimerism levels, 86% (95% CI, 70%–100%). Fifteen engrafted patients discontinued immunosuppression medication with continued stable donor chimerism and no graft-vs-host disease. The normalized hemoglobin and resolution of hemolysis among engrafted patients were accompanied by stabilization in brain imaging, a reduction of echocardiographic estimates of pulmonary pressure, and allowed for phlebotomy to reduce hepatic iron. The mean annual hospitalization rate was 3.23 (95%CI, 1.83–4.63) the year before, 0.63 (95% CI, 0.26–1.01) the first year after,0.19 (95% CI, 0–0.45) the second year after, and 0.11 (95%CI, 0.04–0.19) the third year after transplant. For patients taking long-term narcotics, the mean use per week was 639 mg (95%CI, 220–1058) of intravenous morphine–equivalent dose the week of their transplants and 140 mg (95% CI, 56–225) 6 months after transplant. There were 38 serious adverse events: pain and related management, infections, abdominal events, and sirolimus related toxic effects. CONCLUSIONS AND RELEVANCE Among 30 patients with sickle cell phenotype with or without thalassemia who underwent nonmyeloablative allogeneic HSCT, the rate of stable mixed...

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Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease

Cited by 449 publications

References 40 publications

Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience

Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience

Reconsideration of Age as a Contraindication for Curative Therapy of Sickle Cell Disease

Nonmyeloablative HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Phenotype

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