scholarly journals Allogeneic Hematopoietic Stem-Cell Transplantation in Patients with GATA 2 Deficiency: Influence of Donor Stem Cell Source and Post-Transplantation Cyclophosphamide

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-38
Author(s):  
Diana X. Nichols-Vinueza ◽  
Nirali N. Shah ◽  
Jennifer Cuellar-Rodriguez ◽  
Thomas R. Bauer ◽  
Katherine R. Calvo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Immune Reconstitution ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Gata2 Deficiency ◽  
Disease Free ◽  
Grade Iii

Background: We recently reported on the single-institution experience with allogeneic hematopoietic stem cell transplantation (HSCT) in 22 consecutive patients with GATA2 deficiency or the MonoMAC syndrome and observed a disease-free survival of nearly 90%. However, despite 10/10 HLA match of matched related donors (MRD) and matched unrelated donors (URD), there was a 25% incidence of grades III-IV acute graft-versus-host disease (GVHD) with tacrolimus/methotrexate (Tacro/MTX). In contrast, there was no grade III-IV acute GVHD in the haploidentical related donor (HRD) recipients, all of whom received GVHD prophylaxis with post-transplantation cyclophosphamide (PT/Cy) followed by tacrolimus/mycophenolate (tacro/MMF). Based on this initial experience, the protocol was subsequently amended to incorporate PT/Cy in all patients. We now report on this expanded cohort of a total of 59 patients, representing the largest experience with HSCT for GATA2 deficiency. Methods: This single-institution study was conducted at the National Institutes of Health Clinical Center between 2013 and 2020 (ClinicalTrials.gov Identifier: NCT01861106). Patients between 12 to 60 years of age were eligible if they had a deleterious mutation in the GATA2 gene, or clinical picture of the MonoMAC syndrome. Although the primary endpoints were engraftment and reversal of the clinical phenotype, a secondary endpoint was added to determine if PT/Cy in the MRD and URD reduced the incidence of grade III-IV aGVHD without compromising the overall and disease-free survival. Immune reconstitution at 100 days, 6, 12, 24, 36 months was analyzed. Results: 59 patients (median age at diagnosis 24 years; IQR 20-32) with GATA2 deficiency or the MonoMAC syndrome underwent allogeneic HSCT. MRD and URD recipients received busulfan for four days (targeted to an AUC 3600-4800) and fludarabine, whereas HRD recipients received two days of low dose cyclophosphamide, 5 days fludarabine, 200cGY total body irradiation, and two or three days of busulfan depending upon the presence or absence of clonal cytogenetic abnormalities. Donor sources included: 11 MRD, 31 URD, and 17 HRD. Median follow-up was 2 years [IQR 1-4], 88% (52/59) are currently alive. Seven deaths have occurred, including: persistent AML (n=1); infection (n=4); poor graft function and cardiac arrest (n=1) and from HPV-associated metastatic cancer (n=1). All of the patients who received HRD transplant are alive. Median time to neutrophil engraftment was 15 days (IQR 13-17) and 19.5 days (IQR 16-25) for platelets. Ninety three percent (55/59) of patients had blood test results after 100 days post-transplant to assess immune reconstitution; eighty one percent (45/55) had normal absolute monocyte counts, 67% (37/55) had normal absolute NK cell counts and 89% (49/55) had normal B cells counts. There was one case of primary graft failure in a recipient of an URD-transplant, and one secondary graft rejection in a recipient of HRD-transplant. Fifty-four percent (32/59) of patients had pre-HSCT myelodysplastic syndrome (MDS), and only two relapsed post-HSCT. Forty two percent (25/59) had abnormal cytogenetics pre-HSCT; amongst 23 patients with serial pre/post bone marrow cytogenetic evaluations, 19 had established normal cytogenetics post-HSCT. Forty five percent (19/42) of MRD/URD patients received Tacro/MTX for GVHD prophylaxis, and 31.5% (6/19) developed grade III-IV acute GVHD (aGVHD). In contrast, 55% (23/42) MRD/URD patients received PT/Cy for GVHD prophylaxis, and none developed grade III-IV aGVHD (p 0.0052). Five percent (1/17) of HRD recipients developed grade III-IV aGVHD. Forty two percent (8/19) of MRD/URD patients who received post-transplant Tacro/MTX had chronic GVHD, 4.3% (1/23) of MRD/URD patients who received PT/Cy developed cGVHD, and 5.8% (1/17) of HRD patients developed cGVHD within the first 2 years post-transplant. Conclusions: Allogeneic HSCT using a busulfan-based regimen in GATA2 deficiency results in nearly a 90% disease-free survival with long-term immune reconstitution. The use of PT-Cy reduced the risk of severe aGVHD and cGVHD and did not increase the risk of relapse or progression of MDS/AML. With earlier recognition of the disease, and the use of PT/Cy more broadly, these results are expected to continue to improve. Disclosures Notarangelo: NIAID, NIH: Research Funding.

Clinical Research of Autologous Hematopoietic Stem Cell Transplantation for Hematological Malignancies and Solid Tumors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5475-5475
Author(s):  
Zhen-qian Huang ◽  
Dong-hua Zhang ◽  
Huo Tan ◽  
Cheng-zhi Zhou ◽  
Dan Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Malignant Lymphoma ◽  
Hematological Malignancies ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free

Abstract Objective: To evaluate the therapeutic effect of autologous hematopoietic stem cell transplantation (AHSCT) on hematological malignancies and solid tumors. Methods: 20 patients with median age of 33.4±11.3 (18–50) years received AHSCT, 7 of them were acute non-lymphoblastic leukemias (ANLL)(CR1 5, CR2 1, refractory/relapse 1), 2 were acute lymphoblastic leukemia (ALL)(CR1 2), 1 was chronic myelogenous leukemia (CML-CP2), 1 was chronic lymphoblastic leukemia(CLL-NR), 6 were malignant lymphoma (CR1 2, CR2 2, NR 2), 1 was multiple myeloma, 1 was breast cancer relapsed after resection 10 years and lung and bone metastases, 1 was small cell lung cancer. 2 or 3 of following agents: Cytarabine(Ara-C)3–4g/m2, Cyclophosphamide (CTX) 4–6g/m2, Etoposide (VP-16) 0.5–1.0g/m2, Semustine (me-CCNU) 300mg/m2, Melphala n(Mel) 140mg/m2, Thiotep a (TSPA) 600mg/m2, Carboplatin (CBP) 1.0g/m2, were combined as conditioning regimen in all patients. Among them 2 patients with ALL accepted additional total body irradiation (TBI). Results: All the patients have reconstituted bone marrow hematopoiesis after transplantation. None of them had the transplantation-related mortality. Among 20 cases, 15 achieved disease free survival (DFS) follow-up 36.5(2–106) months. Conclusion: AHSCT might represent an effective approach for the treatment of some patients with chemosensitive solid tumor who are complete remission or part remission. Without compatible donors, patients with leukemia and malignant lymphoma at CR1 stage could receive AHSCT to reduce relapse and increase disease-free survival. It is suggest that have a obvious survival benefit from AHSCT.

Quadruple Therapy with CsA, MTX, MMF and ATG and Triple Therapy with CsA, MTX and ATG for Preventing Graft-Versus-Host Disease in Unrelated Donor Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5296-5296 ◽  
Author(s):  
Zhiping Fan ◽  
Zhengshan Yi ◽  
Qifa Liu ◽  
Jing Sun ◽  
Dan Xu ◽  
...  
Keyword(s):  
Triple Therapy ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Genetic Loci ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Significant Difference ◽  
Disease Free

Abstract Objective To explore the effective protocol for graft-versus-host disease (GVHD) prophylaxis in unrelated donor hematopoietic stem cell transplantation (URD-HSCT). Methods 31 patients with leukemia received URD-HSCT, of whom 16 received quadruple therapy (quadruple group) with CsA, MTX, MMF and ATG for GVHD prophylaxis and 15 received triple therapy (triple group) with CsA, MTX and ATG. 22 patients were matched in all HLA genetic loci with donors, seven were mismatched in one HLA genetic locus, 1 in two HLA genetic loci, and 1 in three HLA genetic loci. Total body irradiation (TBI) plus cyclophosphamide (CTX) was adopted in 17 cases and modified BuCY conditioning regimen (hydroxyurea, busulfan, Ara-C, Cyclophosphamide) in the other 14 cases. Immune reconstitution of quadruple group and triple group at 1,3, 6, 9,12 month after transplantation were examined by flow cytometer, and the diference of the two group were estimated with Independent-Samples T test. The incidence of GVHD of the two group was esitimated with Mann-Whitney Test. Kaplan-Meier survival analysis model was used to estimate the overall survival and the disease-free survival (DFS). Results Immune reconstitution after transplantation of quadruple group and triple group have no significant difference (P>0.05). Acute GVHD (aGVHD) occurred in 9 patients (56.25%) of the quadruple group and in 11 (73.33%) of the triple group, respectively. The incidence of acute GVHD (aGVHD) differed little between the two group (P=0.238). The incidence ofIII~IV°aGVHD in the two group were 6.30% and 26.67%, respectively, and there was no significant difference (P=0.122). 6 patients had chronic GVHD (cGVHD), in the16 cases who could be followed up in quadruple group, 3 of the 11 patients who could be followed up in triple group developed cGVHD postoperatively (P=0.580). Four patients of quadruple group died of hemorrhagic cystitis, mycotic pneumonia, tuberculosis and relapse, respectively. 3 patients of triple group died of GVHD, and the other 3 died of GVHD associated interstitial pneumonia, cytomegalovirus (CMV) pneumonia and pneumocystis carinii infection. The lethality of GVHD of quadruple group and triple group were 0%,26.7%, respectively, and there was significant difference(P=0.027). The one-year disease-free survival rate was 75% and 60% in patients of the quadruple and the triple group, respectively, and significant difference was not noted (P= P=0.188). Conclusion Compared with triple therapy with CsA, MTX and ATG, CsA+MTX+MMF+ATG procedure dose not worsen the immune reconsititution after transplantation. It can’t decrease the incidence and severity of aGVHD, but can lower the lethality of GVHD in URD-HSCT. The quadruple procedure may lead to higher relapse rate after URD-HSCT.

A Novel Chemotherapy-Based Allogeneic Hematopoietic Stem Cell Transplant Regimen for Very Young Children with Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3149-3149
Author(s):  
Susan E. Prockop ◽  
Nancy A. Kernan ◽  
Elizabeth G Klein ◽  
Rachel Kobos ◽  
Andromachi Scaradavou ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Young Children ◽  
Cord Blood ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant

Abstract Abstract 3149 Young children in need of allogeneic hematopoietic stem cell transplant (HSCT) are at increased risk of unacceptable side effects from total body irradiation (TBI) and have historically been considered candidates for non-TBI containing regimens. However, disease free survival (DFS) has been poorer in cohorts of very young patients transplanted without TBI and novel chemotherapy based regimens are needed. We report results in a cohort of 14 children all under three years of age at the time of transplant (6 – 32 months; median 19.8 months) using a clofarabine-based ablative regimen. Fourteen patients in this age group have undergone transplant with a regimen consisting of clofarabine 20 mg/m2/day × 5, thiotepa 10 mg/Kg/day × 1 and melphalan 70 mg/m2/day × 2. All patients had high risk disease. Seven (7) pts were transplanted for ALL, 6 for AML and 1 for JMML. Patients with ALL or AML in first remission (CR1) or CR2, were categorized as patients with good risk disease while all other pts were considered as poor risk irrespective of all other factors. Transplant risk was good for 6/7 with ALL, and 3/6 with AML. The patient with JMML had stable disease. Stem cell grafts consisted of unmodified bone marrow (BMT) (N=6), double cord blood (dCBT) (N=7) and T cell depleted PBSCT (N=1). Donors were matched unrelated (N=5) or mismatched unrelated (N=9) including 7 double umbilical cord blood grafts, and one T cell depleted graft. Graft versus host disease (GvHD) prophylaxis was with tacrolimus and methotrexate for unmodified BMT, tacrolimus and mycophenolate for dCBT or T cell depleted HSCT. Two patients died early post transplant of infection (1) and acute GvHD (1). Neutrophil engraftment for the 13 evaluable patients was at a median of 13 days (10 –29 days) for PBSC and BM grafts and 17.5 days (12 –23 days) for recipients of CB grafts. Platelet engraftment for the 12 evaluable patients was at a median of 23 days (16 – 36 days) for recipients of PBSC and BM grafts and 43.5 days (36 –66 days) for recipients of CB grafts. In all five patients developed grade II-IV GvHD, and two patients chronic GvHD. Seven patients developed transaminitis which resolved in all cases. No patients developed Grade IV mucositis. One patient (AML) died after relapsing 5.5 months post transplant. Two patients are alive after relapsing at 1.3 months (AML) and 10.8 months (JMML) post-transplant. Nine of the 14 patients are alive in continuous complete remission seven of whom are greater than 36 months from transplant (40.2 – 71 months). The seven patients without chronic GvHD have had robust immune reconstitution, have responded to vaccination, and continue to meet growth and developmental milestones. Only one patient (transplanted at 14 months of age) has mild neurocognitive deficits. This novel chemotherapy based regimen is associated with durable engraftment of unmodified and cord blood HSCT grafts and promising disease free survival in very young children with leukemia. Based on the low toxicity profile in this cohort of patients higher dosing of clofarabine will be explored as a possible way to improve leukemia remission in the highest risk patients. Disclosures: Off Label Use: Clofarabine.

Disease-Free Survival Of Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation Is Not Associated With Disease Status and Donor Sources

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2158-2158
Author(s):  
Yue Lu ◽  
Tong Wu ◽  
Xing-Yu Cao ◽  
Yan-Li Zhao ◽  
De-Yan Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Disease Status ◽  
Refractory Anemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free ◽  
Related Mortality

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is an only curative modality currently for myelodysplastic syndrome (MDS). High-risk MDS usually has lower complete remission (CR) rate and higher chemotherapy-related mortality compared with de novo acute myeloid leukemia (AML). To examine whether CR before HSCT has survival benefit for MDS treated by HSCT, we retrospectively analyzed the data during 11 years from our center. The clinical outcomes of MDS after HSCT from different donor sources have also been evaluated. Objective In present clinical study, the effects of disease status and donor sources on disease-free survival (DFS) of MDS after HSCT were studied. Methods From August 2001 to December 2012, total 122 patients with MDS that underwent HSCT in our center were enrolled. Male to Female was 76: 46. The median age was 35 (8 to 57) years old. The median blasts in bone marrow (BM) before conditioning were 9% (1% to 65%). According to 2008 WHO classification, the patients were diagnosed as refractory cytopenias with unilineage dysplasia (RCUD) in 12, refractory anemia with ring sideroblasts (RARS) in 2, 5q- in 1, refractory cytopenias with multilineage dysplasia (RCMD) in 15, refractory anemia with excess blasts (RAEB) -1/RAEB-2 in 36 and transformed AML in 56. For International Prognostic Scoring System (IPSS), 12 patients were in low-risk, 27 in intermediate-1, 24 in intermediate-2, and 59 in high-risk. Based on BM blast percentage pre-conditioning, 47 cases were less than 5%, 43 patients were between 5% to 20%, and 32 cases were more than 20%. The stem cells were from identical siblings (45) or unrelated donor (24) or haploidentical family members (53). Conditioning regimens were BUCY/BUFLU for identical sibling HSCT, and BUCY/BUFLU plus ATG (Thymoglobuline, 8-10mg/kg) for unrelated or haploidentical transplants. Graft-versus-host disease prophylaxis was employed by Cyclosporin A, Methotrexate and Mycophenolate mofetil as reported previously (DP Lu et al., Blood 2006; 107:3065). Results: With median follow-up 31 (1-144) months, DFS was 73.8%. Fourteen patients (11.4%) relapsed. Transplant-related mortality was 14.8%. No significant differences on DFS were found among RCUD/RARS/5q- (68.8%), RCMD (85.7%), RAEB-1/RAEB-2 (72.2%) and transformed AML (73.2%) (p=0.761). A similar DFS was seen in different risk categories (73.3% in low-risk, 79.2% in intermediate-1, 75.0% in intermediate-2 and 71.2% in high-risk; p=0.861). Moreover, CR or not before HSCT has no remarkable effect on DFS (blasts <5%, 78.7%; blasts 5% to 20%, 67.4%; blasts > 20%, 75.0%; p=0.342). Donor sources have also no significant effects on DFS (identical sibling 75.6%, unrelated donor 79.2%, haploidentical family member 69.8%; p=0.651). Conclusions Our clinical results have shown that under current protocol, DFS of MDS after allogeneic HSCT is quite encouraging no matter the disease status and stem cell donor sources. Therefore, it is not necessary that complete remission is achieved by chemotherapy before transplant. Haploidentical family member is an important alternative donor for patients with MDS when matched either identical sibling or unrelated donor is not available. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Improvement of Survival in JMML By Induction Regimen of Decitabine + Cytarabine + Fludarabine before Hematopoietic Stem Cell Transplantation: Study of 33 Cases in Single Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4267-4267
Author(s):  
Xiaoqin Feng ◽  
Zhiyong Peng ◽  
Yuelin He ◽  
Chunfu Li ◽  
Yongsheng Ruan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Free Survival ◽  
Costal Margin ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free

OBJECTIVE: Pre-transplant chemotherapy can control progression of primary disease, alleviate disease and improve disease-free survival after transplantation in juvenile granulocyte leukemia (JMML).Methylation abnormalities play an important role in the development of JMML. This study was to explore the effectiveness of induction regimen including decitabine ,cytarabine and fludarabine before transplantation and to explore the affection to transplantation in JMML. METHODS: A retrospective analysis of the remission and survival of 33 children with JMML before and after stem cell transplantation in the Department of Pediatrics of Nanfang Hospital from 2014.2 to 2019.7. There were fourteen girls and 19 boys, median diagnosis age 23 months(2m-10 years old). Median white blood cell count,median hemoglobin level,median platelet count( WBC) was 29.3G/L (6.29-158.66G/L); 83g /L(41-113g/L,); 27.17G / L(4-431G / L) respectively. Median Hemoglobin F level was 34.16%( 1.56-78%). Median spleen level under the costal margin was 5cm(0-13.3cm); Median liver under the costal margin was 3.9 cm(0 -8.9 cm) .There were 26 cases with the pulmonary involvement (26/33, 78.8%). The original blast cells in bone marrow were 0-8.8%, with a median of 4.5%.Mutant genes including: 2 cases of KAS, 9 cases of NF1, 2 cases of NRAS, 16 cases of PTPN11, and 4 cases without common JMML gene .The first course of treatment after diagnosis is 20 mg/m2 × 5 days of decitabine. The second course of treatment is DA: decitabine 20 mg/m2 × 5 days + cytarabine 100 mg/m2 × 5 days or A-3V regimen: Ara-C 100 mg/m2/d CIV×7 days+Etoposide 100 mg/m2/d ×5 days+Vincristine 1.5 mg/m2/d ×1 day. The third course of treatment is decitabine 20 mg/m2 × 5 days,then FLAG regimen: Fludarabine 30mg / m2 × 5 days, Ara-C 1 g / m2 × 5 days, G-CSF 5μg / Kg × 6 days. Single drug of decitabine 20 mg/m2 × 5 days was adminstered 1-3 times per monthly during the period of waiting for transplantation. Comprehensive assessment was performed before transplantation. Survival outcomes were analyzed by Kaplan-Meier curves. RESULTS: At least 3 courses of chemotherapy were completed in 33 cases, including 1-5 courses of decitabine.The bone marrow was evaluated in 31 patients before transplantation: 12 patients got complete remission(CR) and 19 patients got partial remission(PR) .Peripheral blood evaluation: 23 cases achieved WBC CR; 17 cases achieved platelet CR, 6 cases achieved platelet PR, 7 cases had no improvement. Eighteen cases of spleen were evaluated, of which only 3 cases were CR, 13 cases were PR, and 2 cases did not improve. Overall assessment, only 1 case achieved CR before transplantation, 1 case did not improve, and 31 cases achieved PR .Allogeneic hematopoietic stem cell transplantation was performed in 33 cases, including 3 cases of nonrelated peripheral blood hematopoietic stem cell transplantation(PB HSCT), 30 cases of complementary transplantation (haploid identical PB HSCT plus non-related cord blood transplantation). The median follow-up time after transplantation was 22m(3-63m).There was no death in the period of chemotherapy before transplantation. Four patients relapsed after transplantation, and One patient died of transplantation related death. Three years EFS was 80.6%. Conclusion: Pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine is safe, effective and feasible. The response rate of treatment is 97.0%, although the complete remission rate before transplantation is low, most of them are partial remission, but the disease-free survival after non-related HSCT or complementary transplantation could reached to 80.6%. These results indicated that pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine was benefit to improved the survival of children with JMML after HSCT. Figure 1 Disclosures No relevant conflicts of interest to declare.

scholarly journals Triple Post-Transplant Cyclophosphamide (PTCY) Based Gvhd Prophylaxis for HLA Matched or HLA Haploidentical Transplants

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4881-4881
Author(s):  
Eugenio Galli ◽  
Elisabetta Metafuni ◽  
Sabrina Giammarco ◽  
Maria Assunta Limongiello ◽  
Idanna Innocenti ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Age Over 60 ◽  
Disease Free ◽  
Related Mortality

Abstract We report a retrospective analysis of 198 consecutive allogeneic stem cell transplant (HSCT) recipients, who received post transplant cyclophosphamide (PTCY), cyclosporine and mycophenolate mofetile as g raft-versus-host-disease (GVHD) prophylaxis. The donor was either HLA matched (n=78) (siblings -32- or unrelated -46) , or a haploidentical relative (HAPLO) (n=120). End points of the study were acute and chronic GVHD, transplant related mortality (TRM), relapse, disease free survival (DFS) and graft versus host and relapse free survival (GRFS). The two groups were comparable except for an older age (49 vs 56 years) in the haplo-HLA group. The diagnosis was mainly acute leukemia (57%), myelofibrosis (21%) or lymphoma (12%). Conditioning was myeloablative in 77% and 73% respectively (p=0.57). Acute GVHD grade II-IV developed in 10% of the HLA matched transplants vs 27% in the HAPLO group (p=0.005). The latter also had more moderate-to-severe cGVHD (4% vs 23%, p&lt;0.001). The cumulative incidence of transplant related mortality (TRM) at 1 year for the HLA matched vs HAPLO patients, was 10% vs 21% (p=0.04) (Fig.1) , with age over 60 years being the major negative predictor in multivariate analysis. Relapse at 1 year was 24% for HLA matched vs 10% for HAPLO transplants (p=0.051) (Fig.1). Disease free survival (DFS) at 1 year was 65% and 68% in matched and HAPLO patients, respectively (p=0.85) (Fig.1) and GRFS 55% vs 49% (p=0.18). In multivariate analysis, age over 60 years was the strongest predictor of DFS and GRFS (HR 1.73, p=0.03 and HR 1,65, p= 0.02). In conclusion: when using the same triple PTCY based GVHD prophylaxis, HLA matched grafts are associated with significantly less acute and chronic GvHD, if compared with HAPLO grafts. There is a trend for reduced TRM at 1 year, especially in chronic myelo-lymphoproliferative disorders, and a trend for increased relapse, resulting in identical disease free survival. Figure 1 Figure 1. Disclosures Laurenti: Gilead: Honoraria; Roche: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

Allogeneic and Matched Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Hematologic Malignancies Using a Modified Reduced Intensity Conditioning Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5324-5324
Author(s):  
Marion Raflores ◽  
James Rossetti ◽  
John Lister ◽  
Richard Shadduck ◽  
John Lech ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Reduced Intensity Conditioning Regimen ◽  
Disease Free ◽  
Related Mortality

Abstract INTRODUCTION:Use of a reduced intensity conditioning regimen (RICR) in hematopoietic stem cell transplant may result in lower treatment related mortality (TRM), less acute graft versus host disease (aGVHD) and better survivability, utilizing the graft versus tumor effect from HSCT. METHODS: Our institution’s original RICR protocol conditioning regimen (Trial A) consists of fludarabine 30 mg/m2 (Day-5 to D-2), melphalan 140–180 mg/m2 (Day -3) and ethyol 910 mg/m2 (Day-3) in addition to mycophenolate mofetil 1 g q12H and tacrolimus(serum level 5–15 ng/ml) beginning Day -3 as immunosuppressive therapy. Transplantation was done using peripheral blood stem cells from the best HLA-antigen match sibling (allo) or matched unrelated donor (MUD). We retrospectively compared transplant data from this original protocol to a modified RICR protocol (Trial B) using a lower dose of melphalan 100mg/m2 and addition of thymoglobulin 2mg/kg/d (D-2 to D0). RESULTS: 46 patients were transplanted in Trial A with median age of 46 years. 25 patients had allogeneic and 21 had MUD transplant. 30 patients were transplanted in Trial B with median age of 44 years. 22 patients had an allogeneic and 8 had a MUD transplant. All patients were heavily pretreated with 13 patients in Trial A and 9 patients in Trial B have undergone at least one previous stem cell transplant. At D30, all patients in Trial B were alive while 11% of patients in Trial A died of treatment related cause. At D100, 51% of patients in Trial A and 70% of patients in Trial B were alive. D100 TRM was 40% in Trial A and 20% in Trial B. Table 1. Treatment Outcome OS(%) TRM (%) RM (%) Trial A Trial B Trial A Trial B Trial A Trial B OS:overall survival TRM:treatment related mortality RM: relapse mortality 30 Days MUD 81 100 19 0 0 0 Allo 96 100 4 0 0 0 Total 89 100 11 0 0 0 100 days MUD 40 63 60 38 0 0 Allo 60 73 24 14 16 14 Total 51 70 40 20 9 10 1 year overall survival was 30% in trial A and 20% in Trial B. 1 year disease free survival (DFS) was 18% in trial A and 13% in Trial B. Table 2. 1 year treatment outcome* Overall Survival(%) Disease Free Survival (DFS) % Trial A Trial B Trial A Trial B *for Trial B, 5 living patients have not yet reached 1 year follow-up MUD 21 13 14 0 Allo 37 23 21 18 Total 30 20 18 13 Incidence of aGVHD≥2 in patients not receiving DLI and alive for more than 30 days post transplant was 56% in Trial A (MUD 67%, Allo50%) and 25% in Trial B (MUD63%, Allo 6%). At D100, aGVHD was the most common cause of death in Trial A while overwhelming sepsis was leading cause of death in Trial B. WBC engraftment with ANC&gt;500 was achieved in 98% of patients in Trial A and 93% of patients in Trial B. Average day of engraftment was 13 days in Trial A and 15 days in Trial B. Platelet engraftment with platelet count at least 20,000 was achieved in 80% of patients in both protocols with average day of engraftment at 18 days in Trial A and 21 days in Trial B. 95% of patients in Trial A had achieved at least 80% donor marrow cells at D100 while only 81% achieved this level of chimerism in Trial B. CONCLUSION: The modified RICR protocol for HSCT is a tolerable regimen which results in a lower incidence of D100 TRM and aGVHD but overall and disease free survival are not improved. Marrow engraftment is achieved although slightly delayed compared to the original protocol.

The Effect of Donor CD4+CD25+ Regulatory T Cells on Hematopoietic and Immune Reconstitution, GVHD and Disease-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2910-2910
Author(s):  
Kai Yang ◽  
Qifa Liu ◽  
Zhiping Fan ◽  
Jing Sun ◽  
Zhengshan Yi
Keyword(s):  
T Cells ◽  
Treg Cell ◽  
Immune Reconstitution ◽  
Disease Free Survival ◽  
Treg Cells ◽  
Cell Group ◽  
P Value ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free

Abstract Objectives To explore the effect of donor CD4+CD25+ regulatory T cells (TReg) on hematopoietic reconstitution, immune reconstitutuion and GVHD in patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods 30 patients were divided into high TReg cell group (TReg≥10.0×106 cells/kg) and low TReg cell group (TReg<10.0×106 cells/kg) according to the number of TReg cells in the grafts. 13 patients were in high TReg cell group and 17 in low TReg cell group. The patients details of the two groups are in the following table. Flow cytometry (FCM) was used to continuously detect the percentage of TReg cells in the graft, T lymphocyte subsets and TReg cells in the recipients’ peripheral blood at different time after allo-HSCT. The hematopoietic reconstitution, immune reconstitution, TReg cell reconstitution, the incidence of GVHD and the disease-free survival were observed in the two groups. Results The reconstitution of WBC and plantelet of high TReg cell group and low TReg cell group were 8.62±2.293 and 8.88±2.713, 12.69±5.736 and 15.18±16.708 days, respectively, and differed little between the two groups (P value was 0.778, 0.613, respectively). The incidence of acute GVHD (aGVHD) in high TReg cell group (15.38%) was obviously lower than that in low TReg cell group (58.82%) (P=0.016). There was significantly negative correlation (r=−0.382, P=0.037) between the number of infused donor TReg cells and severity of aGVHD. The reconstitution of CD4+CD3+T, CD45RO+CD4+T cells at 15 days and CD3+T, CD4+CD3+T cells at 30 days in high TReg cell group were notably faster than those in low TReg cell group after allo-HSCT (P value was 0.039, 0.024, 0.014, 0.020, respectively). The reconstitution of TReg cells at 15 and 180 days were significantly faster than those in low TReg cell group after allo-HSCT (P value was 0.013, 0.005, respectively). The 2-year disease-free survival of high TReg cell group and low TReg cell group were (69.90±15.50)% and (85.60±9.50)%, respectively, and there were no significantly difference between the two groups (P=0.514). Conclusion TReg cells could contribute to decreasing the incidence of aGVHD, promoting immune reconstitution and TReg cells reconstitution.

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