Haploidentical T-cell alpha beta receptor and CD19–depleted stem cell transplant for Wiskott-Aldrich syndrome

Kharya, Gaurav; Nademi, Zohreh; Leahy, T. Ronan; Dunn, J.; Barge, D; Schulz, Ansgar; Cant, Andrew J.; Gennery, Andrew R.; Slatter, Mary

doi:10.1016/j.jaci.2014.04.041

Cited by 37 publications

(23 citation statements)

References 9 publications

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“…Handgretinger [5] showed that TCRab þ depletion technology guarantees a fast immune reconstitution. In our study the kinetics of immune reconstitution parameters, including naive T cell counts, were consistent with our expectations and the reports of other researchers [4,7]. Based on our preliminary data, there was no significant difference between MMRD and MUD HSCT.…”

Section: Discussionsupporting

confidence: 93%

“…More recently, a case series of TCRab-depleted haploidentical transplantation in patients with PID was reported from different clinical groups [4,7]. Here, we share our preliminary results on TCRab/CD19-depleted transplantation from MMRDs and MUDs in patients with PID.…”

Section: Introductionsupporting

confidence: 76%

“…There are encouraging reports of a small series of patients with hematologic malignancies and nonmalignant disorders who were transplanted with stem cells from MMRDs by using this approach [4][5][6][7]. T cells with ab-chain TCRs are the major inducers of GVHD, and their elimination from the graft decreases the frequency of this complication [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes

Balashov

Shcherbina

Maschan

et al. 2015

Biology of Blood and Marrow Transplantation

142

105

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The transplantation of stem cells from a matched unrelated donor (MUD) or a haploidentical mismatched related donor (MMRD) is a widely used variant of curative treatment for patients with primary immunodeficiency (PID). Currently, different strategies are used to reduce the risk of post-transplant complications and enhance immune reconstitution. We report the preliminary results of MUD and MMRD transplantation with TCRαβ/CD19 depletion in patients with PID (trial registered at www.clinicaltrials.gov as NCT02327351). Thirty-seven PID patients (median age, 2.6 years; range, .2 to 17) were transplanted from MUDs (n = 27) or haploidentical MMRDs (n = 10) after TCRαβ(+)/CD19(+) graft depletion. The median numbers of CD34(+) and TCRαβ(+) cells in the graft were 11.7 × 10(6)/kg and 10.6 × 10(3)/kg, respectively. Acute graft-versus-host disease (GVHD) was observed in 8 patients (22%), without a statistically significant difference between MUDs and MMRDs; 7 of these patients had grade II acute GVHD and responded to first-line therapy, whereas 1 patient had grade IV acute GVHD with transformation to extensive chronic GVHD. Primary and secondary graft failure (nonengraftment or rejection) was observed in 10 patients (27%), 9 of whom were treated with 1 alkylating agent in the conditioning regimen. All these patients were successfully retransplanted with different rescue protocols. Preliminary data on immune reconstitution were very encouraging. Most patients had significant numbers of T lymphocytes detected on the first assessment (day +30) and more than 500 T cells/μL, on day +120. Based on our preliminary data, no significant difference was seen between MMRD and MUD hematopoietic stem cell transplantation (HSCT). With a median follow-up period of 15 months, the cumulative probabilities of overall patient survival and transplant-related mortality were 96.7% and 3.3%, respectively. Based on the results, the ability to control the main post-transplant complications and the immune reconstitution rates are the main factors leading to successful outcome in patients with PID after TCRαβ(+)-depleted HSCT.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

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Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes

Balashov

Shcherbina

Maschan

et al. 2015

Biology of Blood and Marrow Transplantation

142

105

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“…However, there are only a few reports of transplantations using haploidentical related donors in DOCK8 deficiency [9,14,15]. The success of haploidentical transplantation in other primary immunodeficiency syndromes suggested the feasibility of this approach in patients with DOCK8 deficiency [16-19]. Paramount to the success of haploidentical HSCT is the ability to prevent graft-versus-host disease (GVHD).…”

Section: Introductionmentioning

confidence: 99%

“…Paramount to the success of haploidentical HSCT is the ability to prevent graft-versus-host disease (GVHD). This can be addressed using in vitro techniques with T cell depletion by CD34 + selection or selective T cell depletion (eg, depletion of T cell receptor, depletion of TCRab + (T cell receptor alpha beta) T cells, associated with depletion of CD19 + B lymphocytes) [19,20]. Alternately, in vivo depletion of T cells can be accomplished by pretransplantation serotherapy [21,22] or by using post-transplantation cyclophosphamide (PT/Cy) [16,23].…”

Section: Introductionmentioning

confidence: 99%

Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide

Shah

Freeman

et al. 2017

Biology of Blood and Marrow Transplantation

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Dedicator-of-cytokinesis 8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplantation (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/Cy) for graft-versus-host disease (GVHD) prophylaxis. Seven patients with DOCK8 deficiency (median age, 20 years; range, 7 to 25 years) received a haploidentical related donor HSCT. The conditioning regimen included 2 days of low-dose cyclophosphamide, 5 days of fludarabine, 3 days of busulfan, and 200 cGy total body irradiation. GVHD prophylaxis consisted of PT/Cy 50 mg/kg/day on days +3 and +4 and tacrolimus and mycophenolate mofetil starting at day +5. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively. All patients attained >90% donor engraftment by day +30. Four subjects developed acute GVHD (1 with maximum grade 3). No patient developed chronic GVHD. With a median follow-up time of 20.6 months (range, 9.5 to 31.7 months), 6 of 7 patients are alive and disease free. Haploidentical related donor HSCT with PT/Cy represents an effective therapeutic approach for patients with DOCK8 deficiency who lack a matched related or unrelated donor.

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Diagnosis and Management of an Infant with Microthrombocytopenia

Rose

Jacobson-Kelly

2020

Pediatric Bleeding Disorders

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Haploidentical T-cell alpha beta receptor and CD19–depleted stem cell transplant for Wiskott-Aldrich syndrome

Cited by 37 publications

References 9 publications

Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes

Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes

Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide

Diagnosis and Management of an Infant with Microthrombocytopenia

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