scholarly journals Auto Hematopoietic Stem Cell Transplantation Combined with Another Target Humanized CAR-T Cells for Refractory/Relapsed B-Cell Non-Hodgkin Lymphoma after Failure of Murinized CD19-CAR-T Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 657-657
Author(s):  
Kai Hu ◽  
Fan Yang ◽  
Rui Liu ◽  
Teng Xu ◽  
Peihao Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
B Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Non Hodgkin Lymphoma ◽  
Car T

Abstract Background: The prognosis of refractory/relapsed aggressive B-cell non-Hodgkin lymphoma (r/r B-NHL) is extremely poor especially for the patients who failed to CD19-Specific chimeric antigen receptor-T (CAR-T) cells therapy.Even sequentially autologous hematopoietic stem cell transplantation(ASCT) could not maintain a durable remission in most patients. Aims: To prolong relapse-free survival, we combined ASCT and another target humanized CAR-T cells to treat r/r B-NHL patients failed to murinized CD19-CAR-T cells therapy with either CD22 or CD20 antigen expression on tumor cell.The safety and efficacy will be evaluated. Methods: From December 2019 to March 2021, 12 patients were enrolled. The median age was 38 (16-68) years old. The diagnosis included DLBCL (n=8) ,BL(n=3) and PMBCL (n=1). The median IPI score was 3 (range,2-4).There were 9 patients(9/12,75%) with extranodal lesions. Six cases(6/12,50%) were with TP53 mutations. The disease status was progressive disease in all patients who failed to multi-line therapies and murinized CD19-CAR-T cells therapy.In order to further reduce the tumor burden, all patients were treated with combined chemotherapy before transplantation. Before the trial, the expression of CD20 and CD22 antigen in tumor tissue was positive confirmed by immunohistochemistry,and the target was selected according to the antigen expression. Conditioning with BEAM-based regimen was applied. The kinetics and function of CAR-T cells was monitored by quantitative PCR and flow cytometry. The efficacy was evaluated by PET-CT every 3 month after transplantation. Results: The autologous peripheral blood stem cells were infused with the median CD34 + cells 3.91(range,0.46-9.46)×10 6/kg.Humanized CAR-T cells with the median 1.85 (range,0.13-3.26)×10 6/kg were infused 2 day after stem cells,including target antigen CD20(7/12,58.3%) and CD22(5/12,41.7%). Cytokine release syndrome (CRS) occurred in 11 cases with 5 cases in grade I, 3 case in grade II and 3 cases in grade III.One case developed immune effector cell-associated neurotoxicity syndrome (ICANS) in grade IV. The peak of cytokine IFN-γ and IL-6 post baseline in patients with grade III CRS were significantly higher than those in patients with grade I-II CRS,especially in ICANS patient.Six cases with grade II and III were relieved with glucocorticoid. The neutrophil and platelets engraftment was achieved in all cases on median days 14 (range,9-22) and 14(range,8-35) respectively post-transplant .Seven cases of bacterial enteritis were seen. Pneumonia occurred in 7 cases.For CAR-T cells expansion,the peak time in vivo was on median 11(range,7-28) days after CAR-T cells infusion.The median peak lever of CAR-T cells was 20.3 (range,0.13-60.4)×10 6/L, which was positively correlated with the number of CART infused. The tumor burden before transplantation was not significantly associated with CAR-T cells expansion.The median duration of CAR-T cells in vivo was 30 days, and the longest lasting time was 139 days post-transplant so far. B-cell aplasia was documented in all cases(7/7,100%) of CD20-CART group and two cases(2/5,40%) of CD22-CART group during the follow-up. With the median follow-up 266 (range,118-565) days, 9/12(75%) patients survived,seven cases(7/12,58.3%) achieved complete remission(CR),2 cases(2/12,16.7%) achieved PD and survival with tumor.Kaplan-Meier survival analysis showed that OS and PFS rates were 71.3% and 66.6% respectively at 9 months after transplantation.Two cases(2/12,16.7%) with BL and one with DLBCL (1/12,8.3%)died of PD.Significantly lower levels of Cumulative CAR T cell levels (AUC) during the first 1 month post transplantation were observed in patients with disease progression compared with those who had durable responses (P<0.0001). Conclusion: CRS is manageable and has no influence on hematopoiesis reconstitution.With current protocol, complication was mild and encouraging disease control was found. ASCT combined with another target humanized CAR-T therapy is a safe and effective salvage strategy for r/r B-NHL after failure of murinized CD19-CAR-T. Long-term follow-up is needed. [Key words] refractory/relapsed B-cell non-Hodgkin lymphoma; failure of CD19-CAR-T; another target CAR-T cell; autologous hematopoietic stem cell transplantation Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of Donor-Derived CD19.CAR-T Cells in Treating Patients That Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4561-4561
Author(s):  
Cheng Zhang ◽  
Lei Gao ◽  
Yao Liu ◽  
Li Gao ◽  
Pei-Yan Kong ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Car T

Background The Chimeric Antigen Receptor T (CAR-T) cells with strong anti-leukemia role can treat relapsed/refractory CD19-positive acute lymphoblastic leukemia (CD19+-ALL) with good outcome. The allogeneic CAR-T cells receives activation signals from both T cell receptor (TCR) and CAR, which may possess stronger activity in anti-leukemia cells. However, the infusion of allogeneic CAR-T cells may cause graft-versus-host disease, which could limit its application after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is still unclear that the role of the donor-derived CAR-T cells in treating relapsed patients after allo-HSCT. In this study, the prospective study was performed to investigate the role of donor-derived CAR-T cells on relapsed patients after allo-HSCT. Methods From April 2016 to March 2019, relapsed patients after allo-HSCT with CD19+-ALL and a Karnofsky score greater than or equal to 60 were enrolled in this study. The donor underwent apheresis for mononuclear cells to construct the CAR-T cells. The bone marrow aspiration every month after CART- cells infusion was carried out for the assessment of disease status by follow cytometry. The chimerism was detected every month after CAR-T cells treatment. Results Eighteen patients enrolled in this study. The median number of infused CAR-T cells was 1.825Í106/Kg. Thirteen patients (13/18=72.22%) reached complete remission (CR) after CAR-T cells treatment. Four patients (4/18=22.22%) had ineffectiveness. One patient died from b uncontrolled bleeding because of low platelet. The patients with blast cells <5% had higher CR. The full chimerism achieved after CART- cells treatment for all patients with the decrease of chimerism at the time of relapse. The median time of follow-up was seven months (ranged from three months to twenty-five months). Three patients with decreased CAR-T cells or chimerism was underwent allogeneic hematopoietic stem cell transplantation or relapsed within six months. The other eleven patients were complete remission with full chimerism or the continual proliferation of CAR-T cells without the second allo-HSCT during our follow-up period. Seventeen patients observed cytokine release syndrome in which six patients with degree III-IV. Two patients developed GVHD in skin and intestinal tract. All patients recovered after management. No other severe complications and death were observed. Conclusion Our results showed that the treatment by donor-derived CAR-T cells for relapsed patients after allo-HSCT is safe and effective. No second transplantation was needed for relapsed patients after allo-HSCT with the treatment of donor-derived CAR-T cells that with good chimerism and continual proliferation of CAR-T cells. However, further clinical trials should be performed to investigate this protocol with larger cases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Study on Use of CAR-T Cells in Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5225-5225
Author(s):  
Jun Liu ◽  
Xu Tan ◽  
Ma Ying-Ying ◽  
Wang Mai-Hong ◽  
Yao Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Car T Cells ◽  
Car T

Abstract Background: The chimeric antigen receptor T (CAR-T) cells have showed strong anti-leukemia role, which can treat or prevent relapse by targeting minimal residual disease for patients undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The infusion of allogeneic CAR-T cells may cause the graft-versus-host disease, which could limit its use during and after allo-HSCT. It is still unclear whether CAR-T cells can be used during and after allo-HSCT. In this study, the use of CAR-T cells in these situation was explored. Methods: Two patients with relapsed/refractory acute lymphoblastic leukemia (ALL) received allo-HSCT, the CAR-T cells was used as a reduced-intensity conditioning regimen. Another three patients with high-risk ALL received preventive infusion of CAR-T cells on days +60 after allo-HSCT. Results: For patients undergone allo-HSCT, the time of peak CAR-T cell proliferation was detected after the first infusion of CAR-T cells on day 7. The engraftment and full donor cell engraftment were established. The disease was in complete remission with negative minimal residual disease, which was undetectable by flow cytometry. No graft-versus-host disease and serious cytokine release syndrome was found. For patients received preventive infusion of CAR-T cells, the CAR-T cells continually survival. No graft-versus-host disease and serious cytokine release syndrome was found. The disease is complete remission for 1-6 months. Conclusion: It is safety and effective for CAR-T cells used in allogeneic hematopoietic stem cell transplantation. Disclosures No relevant conflicts of interest to declare.

scholarly journals CNS relapse of B-lymphoblastic lymphoma after allogeneic hematopoietic stem cell transplantation: therapy with donor CD19-specific CAR-T cells

2021 ◽  
Vol 20 (2) ◽  
pp. 143-147
Author(s):  
O. O. Molostova ◽  
L. N. Shelikhova ◽  
D. E. Pershin ◽  
A. M. Popov ◽  
M. E. Dubrovina ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Lymphoma ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Car T ◽  
B Lymphoblastic Lymphoma

Presently, there is no consensus on the best treatment for relapsed B-cell acute lymphoblastic leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in patients with extramedullary lesions. There are certain anti-tumor drugs that can be used in case of relapse after allo-HSCT, however, prospective randomized studies directly comparing different chemotherapy and immunotherapy approaches are generally lacking. Retrospective studies exploring therapy for relapsed disease are difficult to compare due to the inhomogeneity of patient populations and the diversity of treatment approaches. In such situations, the treatment choice is influenced by the characteristics of the tumor population, particularly, its immunophenotype, available drugs, and the experience of a healthcare facility and physicians. This clinical case report describes the process of treating a patient with B-lymphoblastic lymphoma and shows the possibility of using donor CD19-specific CAR-T cells as a treatment for isolated CNS relapse after allo-HSCT. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

scholarly journals Efficacy and Safety of JWCAR029 in Adult Patients with Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4187-4187 ◽  
Author(s):  
Zixun Yan ◽  
Wen Wang ◽  
Zhong Zheng ◽  
Ming Hao ◽  
Su Yang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Dose Level ◽  
Car T Cells ◽  
Car T Cell ◽  
Non Hodgkin Lymphoma ◽  
Car T

Abstract Introduction JWCAR029 is a novel CD19-directed 4-1BB stimulated chimeric antigen receptor T (CAR-T) cell type, which is different from JWCAR017 with independent production of CD4 and CD8 T cells and transfusion in non-fixed ratio. We conducted a single arm, open-label, dose escalation Phase I trial of JWCAR029 in relapsed and refractory B-cell non-Hodgkin lymphoma (NCT03355859). Methods From January to July 2018, 10 patients have been enrolled in this trial, including eight diffused large B cell lymphoma (DLBCL) and two MALT lymphoma, with median age of 47 years (range 32 to 59 years). All the patients received immunochemotherapy as induction and more than two lines of salvage treatment. Two patients received bridging chemotherapy after T-cell collection due to rapid tumor progression, followed by re-evaluation before CAR-T cell infusion. Lymphodepletion preconditioning was accomplished by fludarabine 25mg/m2/d and cyclophosphamide 250mg/m2/d on Day-4 to D-2, followed by CAR-T cell infusion on Day0. JWCAR029 was administrated as a single infusion in escalation dose levels, from 2.5×107 CAR-T cells (dose level 1, DL1) to 5.0×107 CAR-T cells (dose level 2, DL2) and to 1.0×108 CAR-T cells (dose level 3, DL3) according to mTPI-2 algorithm. Circulating blood count, serum biochemistry, and coagulation status were follow-up after infusion. Cytokines were assessed on a Luminex platform. Tumor evaluation was performed on Day 29 by PET-CT. PK data were detected by flow cytometry and real-time quantitative polymerase chain reaction system. All the adverse events were recorded. The study was approved by the Shanghai Rui Jin Hospital Review Board with informed consent obtained in accordance with the Declaration of Helsinki. Results The demographic characteristics of the patients were demonstrated in Table 1. Among six evaluable patients (3 of DL1 and 3 of DL2), the ORR was 100% on Day 29, including four complete remission and 2 partial remission. Cytokine release syndrome (CRS) was 100% in Gr 1, with main symptoms as fever (<39.0 degrees), fatigue, and muscle soreness. No neurotoxicity was observed. Four of the six patients with fever >38.0 degrees used prophylactic IL-6 Inhibitor (8mg/kg, ACTEMRA, two patients administered twice). No patients received steroids. The CRS showed no difference between dose level groups (p>0.99). Adverse effects included leukopenia (Gr 3-4: 83.3%, Gr 1-2: 16.7%), hypofibrinogenemia (Gr 1: 16.7%, Gr 2-4: 0%), liver dysfunction (Gr 1: 33.3%, Gr 2-4: 0%), elevated CRP (Gr 1: 83.3%, Gr 2-4: 0%), ferritin (Gr 1-2: 83.3%, Gr 2-4: 0%), or IL-6 (Gr 1-2:100%, Gr 3-4: 0%, Table 2). Conclusion Although long-term follow-up was needed, the preliminary data of six patients in this trial have demonstrated high response rates and safety of JWCAR029 in treating relapsed and refractory B-cell non-Hodgkin lymphoma. Disclosures Hao: JW Therapeutics: Employment, Equity Ownership.

Allogeneic T-Cells Expressing an Anti-CD19 Chimeric Antigen Receptor Cause Remissions of B-Cell Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation without Causing Graft-Versus-Host Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 99-99 ◽  
Author(s):  
Jennifer N Brudno ◽  
Robert Somerville ◽  
Victoria Shi ◽  
Jeremy J. Rose ◽  
David C. Halverson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
B Cell ◽  
B Cell Malignancies ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T ◽  
Peak Blood

Introduction Progressive malignancy is the leading cause of death after allogeneic hematopoietic stem cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies are often treated with infusions of unmanipulated donor lymphocytes (DLIs) from the transplant donor. DLIs are frequently not effective at eradicating malignancy, and DLIs often cause graft-versus-host disease (GVHD), which is a potentially lethal allogeneic immune response against normal recipient tissues. Methods We conducted a clinical trial of allogeneic T cells that were genetically engineered to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. The CAR was encoded by a gamma-retroviral vector and included a CD28 costimulatory domain. Patients with B-cell malignancies after alloHSCT received a single infusion of CAR T cells. No chemotherapy or other therapies were administered. The T cells were obtained from each recipient's alloHSCT donor. Findings Eight of 20 treated patients obtained remissions, including 6 complete remissions (CR) and 2 partial remissions. The response rate was highest for acute lymphoblastic leukemia with 4/5 patients obtaining minimal-residual-disease-negative CRs, but responses also occurred in chronic lymphocytic leukemia (CLL) and lymphoma. The longest ongoing CR is 30+ months in a patient with CLL. No patient developed new-onset acute GVHD after CAR T-cells were infused. Toxicities included fever, tachycardia, and hypotension. Median peak blood CAR T-cell levels were higher in patients who obtained remissions (39 CAR+ cells/mL) than in patients who did not obtain remissions (2 CAR+ cells/mL, P=0.001). Presence of endogenous normal or malignant blood B lymphocytes before CAR T-cell infusion was associated with higher post-infusion median blood CAR T-cell levels (P=0.04). Compared to patients who did not obtain a remission of their malignancies, patients obtaining remissions had a higher CD8:CD4 ratio of blood CAR+ T cells at the time of peak CAR T-cell levels (P=0.007). The mean percentage of CAR+CD8+ T cells expressing the programmed cell death-1 (PD-1) protein increased from 12% at the time of infusion to 82% at the time of peak blood CAR T-cell levels (P<0.0001). The mean percentage of CAR+CD4+ T cells expressing PD-1 increased from 32% at the time of infusion to 91% at the time of peak blood CAR T-cell levels (P<0.0001). Interpretation Infusion of allogeneic anti-CD19 CAR T cells is a promising approach for treating B-cell malignancies after alloHSCT. Our findings point toward a future in which antigen-specific T-cell therapies will be an important part of the field of allogeneic hematopoietic stem cell transplantation. Table. PatientNumber Malignancy Transplant type Total T cellsinfused/kg Anti-CD19CAR-expressingT cells infused/kg Malignancyresponseat last follow-up(interval from infusion to last follow-up in months) 1 CLL URD 10/10 HLA match 1x106 0.4x106 SD (3) 2 DLBCL Sibling 2x106 0.7x106 SD (1) 3 CLL Sibling 4x106 2.4x106 PD 4 DLBCL Sibling 4x106 2.2x106 SD (31+) 5 CLL URD 10/10 HLA match 1.5x106 1.0x106 CR (30+) 6 MCL Sibling 7x106 4.6x106 SD (3) 7 CLL URD 10/10 HLA match 1x106 0.7x106 PD 8 MCL Sibling 7x106 3.9x106 SD (24+) 9 MCL URD 10/10 HLA match 4x106 2.2x106 PR (3) 10 MCL Sibling 10x106 7.8x106 SD (2) 11 CLL URD 9/10 HLA match 5x106 3.1x106 PR (12+) 12 ALL Ph+ Sibling 7x106 5.2x106 MRD-negative CR (15+) 13 MCL Sibling 10x106 7.1x106 SD (9) 14 ALL Ph-neg Sibling 10x106 7.0x106 MRD-negative CR (5) 15 ALL Ph-neg Sibling 10x106 6.9x106 MRD-negative CR (3) 16 ALL Ph-neg Sibling 7x106 5.6x106 PD 17 DLBCL Sibling 10x106 8.2x106 CR (6+) 18 DLBCL Sibling 10x106 3.1x106 SD (2) 19 FL transformed to DLBCL URD 10/10 HLA match 5x106 4.3x106 PD 20 ALL Ph-neg URD 9/10 HLA match 5x106 4.2x106 MRD-negative CR (3+)^ CLL, chronic lymphocytic leukemia; ALL Ph+, Philadelphia chromosome positive acute lymphoblastic leukemia; ALL Ph-neg, Philadelphia chromosome negative acute lymphoblastic leukemia; MCL, mantle cell lymphoma; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; Sibling, human leukocyte antigen-matched sibling donor; URD, unrelated donor; HLA, human leukocyte antigen; PD, progressive disease; SD, stable disease; PR, partial remission; CR, complete remission; MRD-negative, minimal residual disease negative. ^Patient 20 underwent a second alloHSCT 3.5 months after anti-CD19 CAR T-cell infusion while in MRD-negative CR. Disclosures Goy: Celgene: Consultancy, Research Funding, Speakers Bureau; Allos, Biogen Idec, Celgene, Genentech, and Millennium. Gilead: Speakers Bureau. Rosenberg:Kite Pharma: Other: CRADA between Surgery Branch-NCI and Kite Pharma.

scholarly journals CAR-T after Stem Cell Transplantation in B-Cell Lymphoproliferative Disorders: Are They Really Autologous or Allogenic Cell Therapies?

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4664
Author(s):  
Ariadna Bartoló-Ibars ◽  
Mireia Uribe-Herranz ◽  
Guillermo Muñoz-Sánchez ◽  
Cristina Arnaldos-Pérez ◽  
Valentín Ortiz-Maldonado ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Lymphoproliferative Disorders ◽  
Hematopoietic Stem ◽  
Cell Therapies ◽  
Car T Cells ◽  
Car T

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the standard treatments for B-cell lymphoproliferative disorders; however, deep relapses are common after an allo-HSCT, and it is associated with poor prognosis. A successful approach to overcome these relapses is to exploit the body’s own immune system with chimeric antigen receptor (CAR) T-cells. These two approaches are potentially combinatorial for treating R/R B-cell lymphoproliferative disorders. Several clinical trials have described different scenarios in which allo-HSCT and CAR-T are successively combined. Further, for all transplanted patients, assessment of chimerism is important to evaluate the engraftment success. Nonetheless, for those patients who previously received an allo-HSCT there is no monitorization of chimerism before manufacturing CAR T-cells. In this review, we focus on allo-HSCT and CAR-T treatments and the different sources of T-cells for manufacturing CAR T-cells.

scholarly journals An X-Linked Hyper-IgM Patient Followed Successfully for 23 Years without Hematopoietic Stem Cell Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Necil Kutukculer ◽  
Neslihan Edeer Karaca ◽  
Guzide Aksu ◽  
Ayca Aykut ◽  
Erhan Pariltay ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Intravenous Immunoglobulin ◽  
Hematopoietic Stem Cell ◽  
Activated T Cells ◽  
Hematopoietic Stem ◽  
Hyper Igm

When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals. For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment modality has to be decided for a particular patient regarding hematopoietic stem cell transplantation or intravenous immunoglobulin replacement therapy with P. jiroveci prophylaxis. A seven-year-old male patient was admitted with recurrent upper and lower respiratory tract infections and recurrent otitis media. His initial immunologic evaluation revealed low IgG and normal IgA and IgM levels with normal lymphocyte phenotyping and inadequate specific antibody responses. He was diagnosed as common variable immunodeficiency and began to receive intravenous immunoglobulin (IVIG) (0.5 gm/kg) with four-week intervals. During follow-up for 23 years under IVIG therapy, he was extremely well and never had severe infections. In 2017, targeted next generation sequencing was performed in order to understand his molecular pathology. A previously described hemizygous c.31C>T(p.Arg11Ter) mutation was found in CD40LG gene. The mother was heterozygous carrier for this mutation and his sister did not have any mutation. Flow cytometric analysis for CD40LG expression on activated T cells showed highly decreased, but not absent, CD40LG expression. In conclusion, diagnostic delay is a clinical problem for patients with CD40LG deficiency, because of low or normal IgM levels, showing that all the hypogammaglobulinemic patients, not only with high serum IgM levels, but also with normal to low IgM levels, have to be examined for CD40LG expression on activated T lymphocytes. Secondly, type of CD40LG mutations leads to enormous interpatient variations regarding serum IgM levels, CD40LG levels on activated T cells, age at diagnosis, severity of clinical findings, and follow-up therapies with or without hematopoietic stem cell therapy.

scholarly journals Infusion of CD30 CAR T Cells Is Safe and Effective As Consolidation Following Autologous Hematopoietic Stem Cell Transplant

2021 ◽  
Vol 27 (3) ◽  
pp. S65-S66
Author(s):  
Marcie L. Riches ◽  
Thomas C. Shea ◽  
Anastasia Ivanova ◽  
Catherine Cheng ◽  
Spencer Laing ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Car T
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