scholarly journals Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients

2021 ◽  
Author(s):  
Wolfgang A. Bethge ◽  
Matthias Eyrich ◽  
Stephan Mielke ◽  
Roland Meisel ◽  
Dietger Niederwieser ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
High Risk Patient ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Multicenter Phase

AbstractHematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αβ/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 106 CD34+ cells/kg and 14.2 × 103 TCRαβ+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαβ/CD19-depleted grafts represents a viable treatment option.

scholarly journals Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis

2019 ◽  
Vol 14 (5) ◽  
pp. 719-727 ◽  
Author(s):  
Xianghua Huang ◽  
Wencui Chen ◽  
Guisheng Ren ◽  
Liang Zhao ◽  
Jinzhou Guo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Lupus Nephritis ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem

Background and objectivesOur study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis.Design, setting, participants, & measurementsFrom July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment.ResultsTwenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33–71) months. The mean number of CD34+ cells was (7.3±3.8)×106/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7–9) and 9 (6–10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60–80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%.ConclusionsAutologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.

Non-Myeloablative Autologous Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 156-156
Author(s):  
Laisvyde Statkute ◽  
Yu Oyama ◽  
Ann Traynor ◽  
Larissa Verda ◽  
Walter G. Barr ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lupus Erythematosus ◽  
Disease Free Survival ◽  
Systemic Lupus ◽  
Hematopoietic Stem

Abstract Manifestations of systemic lupus erythematosus (SLE) may in most patients be ameliorated with medications that suppress the immune system. Nevertheless, there remains a subset of SLE patients for whom current strategies are insufficient to control disease. Here we report results of autologous non-myeloablative hematopoietic stem cell transplantation single arm trial performed at Northwestern University Feinberg School of Medicine between February 1997 and January 2005 involving 50 patients with SLE refractory to standard immune suppressive therapies and either organ- or life-threatening visceral involvement. Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) and G-CSF (5 ug/kg/day), enriched ex vivo by CD34+ immunoselection, cryopreserved, and reinfused after treatment with cyclophosphamide (200 mg/kg) and equine anti-thymocyte globulin (90 mg/kg). The primary endpoint was survival, both overall survival and disease free survival. Secondary endpoints include systemic lupus erythematosus disease activity index (SLEDAI), serology (ANA and antids DNA), complement (C3 and C4), and changes in renal and pulmonary organ function assessed pre-treatment and 6 months, 12 months and then yearly for 5 years. Fifty patients were enrolled and underwent stem cell mobilization. Two patients died after mobilization, one from disseminated mucormycosis and another from active lupus after postponing the transplant for 4 months. Forty-eight patients underwent lupus non-myeloablative hematopoietic stem cell transplantation with no treatment related mortality. By intention to treat, treatment related mortality was 2% (1/50). With a mean follow-up of 29 months (range 6 month to 7.5 years ), overall survival was 84%, and probability of disease free survival at 5 years post transplant was 50%. Secondary analysis demonstrated stabilization of renal function and statistically significant improvement (p ≤ .05) in SLEDAI, ANA, anti-ds DNA, complement, and DLCO adjusted for hemoglobin (DLCOadj). In treatment refractory SLE, autologous non-myeloablative hematopoietic stem cell transplantation results in marked amelioration of disease activity, long term disease remission, improvement in serologic markers, and either stabilization or reversal of organ dysfunction.

Phase I Study of Ipilimumab (Neutralizing Monoclonal Anti-CTLA4 Antibody) To Treat Relapse of Malignancy after Allogeneic Hematopoietic Stem Cell Transplantation: Evidence of Tumor Regression without Induction of GVHD.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 410-410
Author(s):  
Asad Bashey ◽  
Bridget Medina ◽  
Sue Corringham ◽  
Mildred Pasek ◽  
Ewa Carrier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Negative Regulator ◽  
Hematopoietic Stem ◽  
Anti Cancer ◽  
Grade 3

Abstract Failure of adoptive cellular immunotherapy is an important cause of relapse of malignancy (RM) and death following allogeneic hematopoietic stem cell transplantation (allo-HCT). CTLA-4 is a negative regulator of activated T-cells. Therapeutic blockade of CTLA-4 has demonstrated potent anti-cancer effects in animal models, and in patients with some solid tumors. Although CTLA-4 blockade may augment graft-versus-malignancy following allo-HCT, GVHD and other immune complications may also be increased. We report the results of a completed phase I dose-escalation trial of a neutralizing human monoclonal anti-CTLA-4 antibody (ipilimumab) in patients with RM following allo-HCT. Eligibility criteria included allo-HCT ≥90 days previously, > 50% donor T-cell chimerism, no prior grade 3/4 GVHD, no prophylaxis/therapy for GVHD for ≥ 6 weeks. Patients received a single dose of ipilimumab over 90 min. (Donor lymphocyte infusion (DLI) at a dose of 5 x 10e6 CD3 cells/kg was allowed 8 weeks following ipilimumab if no GVHD occurred and malignancy was present. Seventeen patients (13M, 4F; median age 42 (21–64); Hodgkin’s disease [HD] =7 Myeloma [MM]=3, CML=2, CLL=1, AML=1, NHL=1, Renal Ca =1, Breast Ca=1; 14 related donors, 3 unrelated; 5 myeloablative, 12 RICT) were treated at three centers (4 at dose-level 1 [DL1] 0.1 mg/kg, 3 at 0.33 mg/kg [DL2], 4 at 0.66 mg/kg [DL3], 3 at 1.0 mg/kg [DL4] and 3 at 3.0 mg/kg [DL5]). Six patients had failed prior DLI. Median time between BMT and ipilimumab was 374 d (125–2368). Seven patients received additional DLI. Ipilimumab was well tolerated in this setting. No DLT was seen at levels up to DL5. No infusional toxicity was seen. No patient developed clinically significant GVHD within 90 days following ipilimumab. One patient developed grade II acute GVHD of the skin 12 weeks following DLI. Two possible immune breakthrough events were documented: grade 3 polyarthropathy 14 weeks following ipilimumab, but also 6 weeks post DLI, which resolved with corticosteroid therapy, (AML, DL1, RhF+ pre- ipilimumab); grade 1 chemical hyperthyroidism with thyroid-stimulating antibody 6 weeks post ipilimumab (CLL, DL3). Two patients developed objective evidence of disease response after ipilimumab alone: regression of refractory lymphadenopathy in a patient with mantle cell NHL lasting 3m [DL4]; CR in a patient with HD ongoing at 2m [DL5].Both patients had failed prior DLI. Two additional patients demonstrated possible anti-cancer effects (reduction of PB and BM blasts in AML, DL1; maintenance of molecular remission in a CML patient given ipilimumab alone for 2.5 yrs despite stopping imatinib, DL1). PK data will be presented. This study shows that clinically active doses of ipilimumab (up to 3.0 mg/kg) can safely be administered to patients with RM following allo-HCT without inducing/exacerbating GVHD. Organ specific immune breakthrough events can be seen as in non-allo-HCT patients.

scholarly journals Hematopoietic stem cell transplantation monitoring in childhood. Hematological diseases in Serbia: STR-PCR techniques

2007 ◽  
Vol 59 (1) ◽  
pp. 23-27
Author(s):  
Aleksandra Krstic ◽  
O. Stojkovic ◽  
Marija Guc-Scekic ◽  
Dragana Vujic ◽  
Dragana Jevtic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Tandem Repeats ◽  
Methodological Approach ◽  
Disease Free Survival ◽  
Mixed Chimerism ◽  
Hematopoietic Stem

Hematopoietic stem cell transplantation (HSCT) is a very successful method of treatment for children with different aquired or inborn diseases. The main goal of post-transplantation chimerism monitoring in HSCT is to predict negative events (such as disease relapse and graft rejection), in order to intervene with appropriate therapy and improve the probability of long-term DFS (disease free survival). In this context, by quantifying the relative amounts of donor and recipient cells present in the peripheral blood sample, it can be determined if engraftment has taken place at all, or if full or mixed chimerism exists. In a group of patients who underwent hematopoietic stem cell transplantation at the Mother and Child Health Care Institute, we decided to use standard human identfication tests based on multiplex PCR analyses of short tandem repeats (STRs), as they are highly informative, sensitive, and fast and therefore represent an optimal methodological approach to engraftment analysis.

Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1616-1623 ◽  
Author(s):  
Aloysius Y. L. Ho ◽  
Antonio Pagliuca ◽  
Michelle Kenyon ◽  
Jane E. Parker ◽  
Aleksandar Mijovic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) has improved the accessibility of transplantation in patients previously ineligible. We report the results of allografting following conditioning with fludarabine, busulphan, and alemtuzumab in 62 patients with myelodysplastic syndromes (MDSs) (matched sibling donors [24] or volunteer unrelated donors [VUDs, 38]). The median age for sibling recipients was 56 years (range, 41-70 years) and for VUD recipients, 52 years (range, 22-65 years), with a median follow-up (survivors) of 524 days (range, 93-1392 days) and 420 days (range, 53-1495 days), respectively. The nonrelapse mortality (NRM) at days 100, 200, and 360 was 0%, 5%, and 5%, respectively, for siblings and 11%, 17%, and 21%, respectively, for VUD. The overall survival at one year was 73% for siblings and 71% for VUDs, with a disease-free survival (DFS) of 61% and 59%, respectively. The prognostic significance of the International Prognostic Scoring System (IPSS) was preserved. Of recipients, 86% achieved full-donor chimerism. The cumulative incidence at day 100 of grades III to IV graft-versus-host disease (GVHD) for VUD recipients was 9% and for sibling recipients, 0%. There were 26 patients (16 sibling and 10 VUD) who received donor lymphocyte infusion (DLI) at a median of 273 days (range, 126-1323 days). RIC allogeneic HSCT using this protocol appears to be safe and permits durable donor engraftment. Longer follow-up is required to confirm any potential survival advantage. (Blood. 2004;104:1616-1623)

Allogeneic Hematopoietic Stem-Cell Transplantation for Myeloid Sarcoma: A Retrospective Study From the SFGM-TC

2008 ◽  
Vol 26 (30) ◽  
pp. 4940-4943 ◽  
Author(s):  
Patrice Chevallier ◽  
Mohamad Mohty ◽  
Bruno Lioure ◽  
Gerard Michel ◽  
Nathalie Contentin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Therapeutic Option ◽  
Disease Free Survival ◽  
Myeloid Sarcoma ◽  
Hematopoietic Stem ◽  
Kaplan Meier

Purpose This retrospective multicenter study assessed the outcome of 51 patients with myeloid sarcoma (MS) who underwent allogeneic hematopoietic stem-cell transplantation (alloHSCT). Patients and Methods Most patients had MS presenting in conjunction with acute myeloid leukemia (AML) or after AML. Six patients had isolated MS. The median time between diagnosis and alloHSCT was 8 months (range, 2.8 to 67). Forty patients were in complete remission (CR) at time of alloHSCT. Results With a median follow-up of 33 (range, 1 to 182) months, the Kaplan-Meier estimates of overall survival (OS) and disease-free survival were 47% (95% CI, 33% to 61%) and 36% (95% CI, 24% to 50%) at 5 years. Twenty patients (39%) relapsed at a median of 204 (range, 35 to 1151) days after alloHSCT, with relapse being the major cause of death. In a Cox multivariate analysis, age ≥ 15 years and remission status at time of alloHSCT (CR v other) were associated with improved OS (hazard ratio [HR], 0.27; 95% CI, 0.12 to 0.65; P = .003; and HR, 0.22; 95% CI, 0.08 to 0.57; P = .002, respectively). Conclusion We conclude that first-line alloHSCT performed early in the course of MS is a valid therapeutic option.

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