CTLA4Ig Primed Donor Lymphocyte Infusion: A Novel Approach to Immunotherapy after Haploidentical Transplantation for Advanced Leukemia

Jaiswal, Sarita Rani; Bhakuni, Prakash; Joy, Aby; Kaushal, Sakshi; Chakrabarti, Aditi; Chakrabarti, Suparno

doi:10.1016/j.bbmt.2018.12.836

Cited by 24 publications

(18 citation statements)

References 37 publications

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“…When previously transplanted patients had >30% blasts in PB or low WBC counts (<1 × 10 9 /L), T cells were obtained from donors. The agent was administered at dosage of ≤4 × 10 6 per kilogram (/kg) of body weight in non-transplanted patients and at dosage of ≤1 × 10 6 /kg for previously transplanted patients (lower dosages of CAR T-cells derived from donor lymphocytes were applied for reducing risk of severe adverse effects [23,24]).…”

Section: Manufacture Of Car T-cellsmentioning

confidence: 99%

CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia

Pan¹,

Niu

Deng³

et al. 2019

Leukemia

184

167

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Despite worldwide promising clinical outcome of CD19 CART therapy, relapse after this therapy is associated with poor prognosis and has become an urgent problem to be solved. We conducted a CD22 CAR T-cell therapy in 34 relapsed or refractory (r/r) BALL pediatric and adult patients who failed from previous CD19 CAR T-cell therapy. Complete remission (CR) or CR with incomplete count recovery (CRi) was achieved in 24 of 30 patients (80%) that could be evaluated on day 30 after infusion, which accounted for 70.5% of all 34 enrolled patients. Most patients only experienced mild cytokine-release syndrome and neurotoxicity. Seven CR patients received no further treatment, and 3 of them remained in remission at 6, 6.6, and 14 months after infusion. Eleven CR patients were promptly bridged to transplantation, and 8 of them remained in remission at 4.6 to 13.3 months after transplantation, resulted in 1-year leukemia-free survival rate of 71.6% (95% CI, 44.2-99.0). CD22 antigen loss or mutation was not observed to be associated with relapsed patients. Our study demonstrated that our CD22 CAR T-cells was highly effective in inducing remission in r/r BALL patients, and also provided a precious window for subsequent transplantation to achieve durable remission.

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Section: Manufacture Of Car T-cellsmentioning

confidence: 99%

CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia

Pan¹,

Niu

Deng³

et al. 2019

Leukemia

184

167

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“…All patients received post-transplant cyclophosphamide as described previously. Along with the introduction of pGI, the graft-versus-host disease (GVHD) prophylaxis protocol was also modified to include CTLA4Ig with either sirolimus (for nonmalignant diseases) [17] or cyclosporine (for malignant diseases) [16]. For patients with malignant diseases, in addition, CTLA4Ig primed donor lymphocyte infusions were administered as described previously [16].…”

Section: Transplant Protocolsmentioning

confidence: 99%

Impact of Preemptive Granulocyte Infusions During Febrile Neutropenia in Patients Colonized with Carbapenem-Resistant Gram-Negative Bacteria Undergoing Haploidentical Transplantation

Jaiswal¹,

Bhakuni²,

Bhagwati

et al. 2019

Biology of Blood and Marrow Transplantation

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We prospectively studied the impact of preemptive granulocyte infusions (pGIs) in 69 patients colonized with carbapenem-resistant gram-negative bacteria (CRGNB) undergoing haploidentical hematopoietic cell transplantation (HCT) compared with a previous cohort of 33 patients who received only antimicrobials directed toward CRGNB at the onset of neutropenic fever (non-pGI group). All patients developed neutropenic fever at a median of day +8 (range, À4 to +12) after transplantation. Engraftment kinetics were similar for both groups. The median number of GIs was 2 (range, 1 to 7), and the median dose of granulocytes infused was 5 £ 10 10 granulocytes per infusion (range, 1 to 30). The overall incidence of CRGNB bloodstream infections (BSIs) was 21.2% in non-pGI group (7/33) and 17.5% (12/69) in the pGI group (P = .8). However, the CRGNB-related mortality among those with BSI was 100% (7/7) in the non-pGI group versus 16.6% (2/12) in the pGI group (P = .001). The day 100 (4.4% versus 24.4%, P = .002) and 2-year nonrelapse mortality (7.5% versus 35.6%, P = .0001) were significantly reduced in the pGI group. The overall survival at 2 years was 75.6% in the pGI group versus 21.2% in the non-pGI group (P = .0001). Colonization and subsequent BSI with CRGNB are associated with a high incidence of mortality in patients undergoing HCT. pGI reduced early mortality associated with CRGNB in colonized patients undergoing post-transplant cyclophosphamideÀbased haploidentical HCT.

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“…Conditioning regimens for malignant and non‐malignant diseases have been described in detail in our previous publications . All patients received PTCy as described previously.…”

Section: Methodsmentioning

confidence: 99%

“…All patients received PTCy as described previously. The methods followed for HLA‐typing, KIR genotyping and defining NK cell alloreactivity, and the mobilization protocol for hematopoietic stem cells (HSC) have been described in our earlier studies …”

Section: Methodsmentioning

confidence: 99%

Rotavirus infection following post‐transplantation cyclophosphamide based haploidentical hematopoietic cell transplantation in children is associated with hemophagocytic syndrome and high mortality

Jaiswal¹,

Bhakuni²,

Chakrabarti³

et al. 2019

Transplant Infectious Dis

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We evaluated the incidences and consequences of rotavirus induced diarrhea in a cohort of 115 patients undergoing T‐cell replete haploidentical transplantation. Four out of 115 patients developed rotavirus‐induced diarrhea between 47 and 147 days. The incidence of rotavirus infection was 9.7% in children compared to none in adults (P = .01). This was 25.3% in those with GVHD compared to 1.2% in those without GVHD (P = .001). Rotavirus infection was followed by post–transplantation hemophagocytic syndrome (PTHPS) at a median of 4 days (range, 3‐10 days) in all four patients. Three patients succumbed to the complications related to PTHPS. Only one patient, who is long‐term survivor, was able to eliminate this virus after 2 weeks. Children undergoing T‐replete haploidentical hematopoietic cell transplantation who develop GVHD are at a higher risk of community‐acquired rotavirus infection which was strongly associated with PTHPS with poor outcome.

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CTLA4Ig Primed Donor Lymphocyte Infusion: A Novel Approach to Immunotherapy after Haploidentical Transplantation for Advanced Leukemia

Cited by 24 publications

References 37 publications

CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia

CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia

Impact of Preemptive Granulocyte Infusions During Febrile Neutropenia in Patients Colonized with Carbapenem-Resistant Gram-Negative Bacteria Undergoing Haploidentical Transplantation

Rotavirus infection following post‐transplantation cyclophosphamide based haploidentical hematopoietic cell transplantation in children is associated with hemophagocytic syndrome and high mortality

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