Infusion of hemolyzed red blood cells within peripheral blood stem cell grafts in patients with and without sickle cell disease

Fitzhugh, Courtney D.; Unno, Hayato; Hathaway, Vincent; Coles, Wynona; Link, Mary E.; Weitzel, R. Patrick; Zhao, Xiongce; Wright, Elizabeth C.; Stroncek, David F.; Kato, Gregory J.; Hsieh, Matthew M.; Tisdale, John F.

doi:10.1182/blood-2011-11-392654

Cited by 4 publications

(4 citation statements)

References 15 publications

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“…In patients with prior pulmonary complications, 300 rad of total-body irradiation and the unmanipulated graft, which contained hemolyzed red blood cells, also did not cause acute pulmonary complications. 34 Over time, there was significant improvement in tricuspid regurgitant velocity, which may reflect the increase in hemoglobin as previously demonstrated in patients with heart failure. 35 Hospitalizations were reduced after transplantation for the entire cohort, as was the use of narcotics.…”

Section: Discussionsupporting

confidence: 53%

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

Hsieh

Fitzhugh

Weitzel

et al. 2014

JAMA

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300

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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Section: Discussionsupporting

confidence: 53%

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

Hsieh

Fitzhugh

Weitzel

et al. 2014

JAMA

Self Cite

300

338

View full text Add to dashboard Cite

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“…However, it is known that washing leads to cell loss . In addition, a study of patients receiving infusions of peripheral blood HPCs demonstrated that the systemic toxicities typically associated with free Hb were not related to free Hb in the product . For these reasons, we did not further manipulate (i.e., wash or volume reduce) the thawed HPC‐A product before infusion.…”

Section: Discussionmentioning

confidence: 99%

Difficulties in hematopoietic progenitor cell collection from a patient with TEMPI syndrome and severe iatrogenic iron deficiency

et al. 2015

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“…This is not well supported by human studies. Recently, Fitzhugh and coworkers showed that infusion of hemolyzed RBCs within the peripheral blood stem cell graft that contained 34.5 ± 6.9 μmol of cell‐free Hb does not significantly change blood pressure but the study could not exclude minor clinical effects. Since the expected level of free Hb in CB infusates is less than 70 μmol (legend of Table ), it is unlikely that such levels would be associated with serious events and therefore may not necessitate wash of CB thaw especially in cases with no factors for infusion toxicity (kidney, pulmonary, bleeding, and/or heart disease and/or hypersensitivity to DMSO, dextran, or plasma proteins).…”

Section: Cb Products and Product Componentsmentioning

confidence: 99%

Current thawing and infusion practice of cryopreserved cord blood: the impact on graft quality, recipient safety, and transplantation outcomes

et al. 2014

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Methods of handling, thawing, and infusion of cord blood (CB) products vary substantially among thaw/transplant centers (TCs). This review 1) compares currently available CB product types and thaw methods recommended by CB banks (CBBs), 2) discusses causes of inconsistency in thaw method application at TCs, 3) advises elements to consider in thaw method approval or selection at the TC, 4) provides a procedural template for the traditional thaw methods, and 5) suggests acceptable time from product thaw to infusion and other considerations for safe infusion. It also compares postinfusion adverse reaction and engraftment data as functions of thaw methods. Remarks and suggestions made throughout this review are: 1) not intended to supersede manufacturer's instructions but meant to support the standardization of preparative procedures recommended by CBBs and 2) intended to help TCs to investigate relevant quality issues and handle challenges, especially when the TC is unable to follow recommendations due to foreseeable technical, quality, and/or clinical factors.

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Infusion of hemolyzed red blood cells within peripheral blood stem cell grafts in patients with and without sickle cell disease

Cited by 4 publications

References 15 publications

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

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

Difficulties in hematopoietic progenitor cell collection from a patient with TEMPI syndrome and severe iatrogenic iron deficiency

Current thawing and infusion practice of cryopreserved cord blood: the impact on graft quality, recipient safety, and transplantation outcomes

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