G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Acute Leukemia Patients in the First Complete Remission: A Registered Study

G-CSF-mobilized peripheral blood (G-PB) harvest is the predominant graft for identical sibling donor and unrelated donor allogeneic hematopoietic stem cell transplantation (HSCT) recipients, but it was controversial in haploidentical related donor (HID) HSCT. In this registry study, we aimed to identify the efficacy of HID G-PB HSCT (HID-PBSCT) for acute leukemia (AL) patients in first complete remission (CR1). Also, we reported the outcomes for the use of G-PB grafts in comparison with the combination of G-BM and G-PB grafts in HID HSCT recipients. Sixty-seven AL patients in CR1 who received HID-PBSCT were recruited at Institute of Hematology, Peking University. Patients who received haploidentical HSCT using the combination of G-BM and G-PB harvests in the same period were enrolled as controls (n=392). The median time from HSCT to neutrophil and platelet engraftment was 12 days (range, 9–19 days) and 12 days (range, 8–171 days), respectively. The 28-day cumulative incidence of neutrophil and platelet engraftment after HSCT was 98.5% and 95.5%, respectively. The cumulative incidences of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) were 29.9% (95%CI 18.8–40.9%) and 7.5% (95%CI 1.1–13.8%), respectively. The cumulative incidences of total and moderate-severe chronic GVHD were 54.9% (95%CI 40.9–68.8%) and 17.4% (95%CI 6.7–28.0%), respectively. The cumulative incidences of relapse and non-relapse mortality were 13.9% (95%CI 5.4–22.5%) and 3.4% (95%CI 0–8.1%), respectively. The probabilities of overall survival (OS) and leukemia-free survival (LFS) were 84.7% (95%CI 74.7–94.7%) and 82.7% (95%CI 73.3–92.1%) respectively. Compared with the HID HSCT recipients using the combination of G-BM and G-PB grafts, the engraftments of neutrophil and platelet were both significantly faster for the G-PB group, and the other clinical outcomes were all comparable between the groups. In multivariate analysis, graft types did not influence the clinical outcomes. Overall, for the patients with AL CR1, G-PB graft could be considered an acceptable graft for HID HSCT recipients. This study was registered at https://clinicaltrials.gov as NCT03756675.

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Outcome of Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia in Third Complete Remission (CR3): A Vital Role for Graft-Versus-Host-Disease/Graft-Versus-Leukemia Effect in Survival.

Blood ◽

10.1182/blood.v108.11.3667.3667 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3667-3667

Author(s):

Adam Gassas ◽

Kashif Ishaqi ◽

John Doyle

Keyword(s):

Stem Cell ◽

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Complete Remission ◽

Lymphoblastic Leukemia ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Graft Versus Host ◽

Related Mortality

Abstract Children with acute lymphoblastic leukemia (ALL) who suffer 2 relapses could be salvaged by hematopoietic stem cell transplantation (HSCT) when a suitable stem cell source is available provided they respond to the pre HSCT chemotherapy and at least enter morphological remission. However, these patients are at very high risk for post HSCT relapse and also at a high risk for transplant related mortality (TRM). Our objective, herein, was to review the outcome of children (0–18years) with ALL who received allogeneic HSCT in third complete remission (CR3) at our institution. Between January 1994 – August 2005, twenty-two consecutive children in CR3 received HSCT in the Hospital for Sick Children, Toronto, Canada. Conditioning regimens included single dose of VP16 (60mg/kg infused over 4 hours) and fractionated total body irradiation (TBI; 1200cGy) in six fractions over 3 days (VP16/TBI) in 10 patients (1994–1998) and cyclophosphamide 50mg/kg infused over 1 hour daily for 4 days followed by the same dose of fractionated TBI (CY/TBI) in 12 patients (1999–2005). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A and a short course of methotrexate for the majority of patients, and all patients were in complete morphological remission prior to HSCT. Median age was 8.4 years (range 3–15.4). Donor source was as follows: matched sibling donor (MSD), 8; matched unrelated donor (MUD) 6; one antigen mismatch related donor (MMRD) 4; one antigen mismatched unrelated donor (MMUD) 3; and one patient received 1 antigen mismatched cord progenitor stem cells. White cell engraftment was successful in all patients at a median of 18 days (range 9–29). Ten patients died of TRM, seven relapsed, one died from other causes and four patients are long term survivors at a median follow up of 3.7 years (range 1–10.2). All patients who did not develop clinical acute or chronic GVHD relapsed and died. Event free survival was (EFS 19% ± 4%). Three out of the 4 survivors received MMUD and all 4 survivors had moderate to severe acute GVHD and three had chronic GVHD, limited in two and extensive in one. Conclusion: Children with ALL in CR3 receiving HSCT are extremely high risk for relapse and transplant related mortality. These children have already relapsed twice and demonstrated chemotherapy resistance and GVL/GVHD plays a key role in leukemia eradication. Although, TRM is high in such patients and GVHD could potentially increase TRM, there are no survivors without GVHD and exploring means of inducing GVHD by reduction of immunosuppressive medications or other means of immunotherapy should seriously be considered in these patients.

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A Phase II Clinical Trial of Post-Transplant Cyclophosphamide for Graft Versus Host Disease Prevention Following Myeloablative Peripheral Blood Stem Cell Matched Unrelated Donor Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood-2019-129536 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2003-2003

Author(s):

Omer Jamy ◽

Racquel Innis-Shelton ◽

Susan Bal ◽

Ravi K. Paluri ◽

Samina Karim ◽

...

Keyword(s):

Stem Cell ◽

Peripheral Blood ◽

Research Funding ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Research Support ◽

Hematopoietic Stem ◽

Entire Cohort ◽

Graft Versus Host ◽

Gvhd Prophylaxis

Background: The use of post-transplant cyclophosphamide (PT-Cy) in combination with other immunosuppressive agents for graft versus host disease (GVHD) prophylaxis in matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. PT-Cy mitigates GVHD after T-cell replete HLA haploidentical (Haplo) bone marrow transplant. Extrapolating from the success of PT-Cy in haplo transplants, we investigated the benefit of PT-Cy (at a lower dose than that used in haplo HSCT) in preventing GVHD following myeloablative peripheral blood stem cell (PBSC) MUD HSCT. Methods: We conducted a phase II clinical trial between September 2013 and June 2018 of PT-Cy for GVHD prophylaxis following myeloablative MUD HSCT. GVHD prophylaxis consisted of 1 dose of PT-Cy 50mg/kg on day +3, mycophenolate mofetil starting day +5 till day +35 and tacrolimus starting on day +5 with taper starting at day +100. The primary endpoint of the study was to determine the incidence of grade II-IV acute GVHD. Secondary endpoints included overall survival (OS), disease free survival (DFS), non-relapse mortlity (NRM) and time to engraftment. Approval for the study was obtained from the Institutional Review Board. Results: There were 39 patients enrolled in the study (Table 1). The mean age of the study population was 47.36 years (SD 13.41). There were 23 females (59%) and majority of the patients were white (85%). Thirty six donors were 8/8 HLA MUD and 3 were 7/8 matched unrelated. The stem cells were collected from peripheral blood in all cases. Indications for HSCT included AML/MDS (62%), ALL (15%), myelofibrosis (10%), NHL/HL (10%) and CML (3%). Based on disease risk index (DRI) assessment, 6 (15%) patients were DRI high, 32 (82%) were intermediate and 1 (3%) was low. The most commonly used myeloablative conditioning regimen was Busulfan and Fludarabine (74%). All 6 patients with ALL received TBI (12 Gy) based conditioning. Three patients with NHL received Fludarabine and Melphalan. There was 1 death within the first 30 days before engraftment. The remaining 38 patients (97%) successfully engrafted. The median time to ANC engraftment was 12 days (range 9-14 days). The incidence of day 100 acute GVHD maximum grade was 36% for grade I/II and 5% for grade III/IV (Table 2). The overall incidence of limited and extensive chronic GVHD was 10% and 36% respectively. There were 8 (21%) confirmed relapses within the first year after HSCT. Twenty four patients were alive at the 1-year mark after transplant and 17 of them were in complete remission. The 1-year and 2-year OS rates were 61.5% and 51.2% respectively. The median OS for the entire cohort was 21.2 months with a median follow up of 50 months (Figure 1). The day 100, 1-year and overall NRM rates were 10%, 28% and 33% respectively with infectious complications being the most common cause of death. Conclusion: We report a low incidence of acute severe GVHD with the combination of one dose of PT-Cy in combination with MMF and tacrolimus following myeloablative PBSC MUD HSCT. The single dose of PT-Cy may explain the modest control over chronic GVHD with this regimen. We also report favorable survival outcomes along with acceptable levels of NRM for the entire cohort. The use of PT-Cy in combination with other immunosuppressant agents for GVHD prevention appears to be a promising strategy in MUD HSCT and may play a vital role in mismatched unrelated donor transplants as well. Disclosures Costa: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; Fujimoto Pharmaceutical Corporation Japan: Other: Advisor; GSK: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy. Saad:Actinium Pharma Inc: Consultancy; Amgen: Other: Research Support; Kadmon: Other: Research Support; OrcaBio: Other: Research Support.

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Autologous Hematopoietic Stem Cell Transplantationfor Adult with Acute Leukemia in First Complete Remission

Blood ◽

10.1182/blood.v112.11.4447.4447 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4447-4447

Author(s):

Huifen Zhou ◽

Wu Depei ◽

Xiaowen Tang ◽

Aining Sun ◽

Zhengming Jin ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Complete Remission ◽

Acute Leukemia ◽

Hematopoietic Stem Cell ◽

Risk Group ◽

Consolidation Chemotherapy ◽

Moderate Risk ◽

Hematopoietic Stem ◽

First Complete Remission

Abstract Objective The objective of this study was to evaluate the clinical outcome of autologous hematopoietic stem cell transplantation (AHSCT) for acute leukemia(AL). Methods The outcome of 56 AL patients who received autologous HSCT(AHSCT) for AL in first complete remission (CR) from May 2001 to May 2008 were analyzed retrospectively. There were 31 males and 25 females, the median age was 25(11~ 57)years. The diagnosis of these patients were acute myeloid leukemia (AML, n=38), acute lymphocytic leukemia(ALL, n=17) and acute hybrid leukemia (AHL, n=1). Patients were divided into low/moderate risk group (n=46) and high risk group (n=10) according to their characteristics of newly diagnosis. If the patient achieved first complete remission(CR), one to three courses of intensification chemotherapy containing high dose cytarabine(HDAC)were given. All the patients were in CR1 before AHSCT. Stem cells were mobilized with MAG regimen which composed of HDAC, Mitoxantrone and G-CSF. The conditioning regimen consisted of modified BU/ CY for AML patients or total body irradiation (TBI) plus cyclophosphamide (CTX) for ALL patients. Patients received consolidation chemotherapy every 3 months after AHSCT until 3 years post transplant. Nine patients received several course of cytokine-induced killer (CIK) cells treatment. Result The median number of MNC and CD34 positive cell was 6.9(1.2 `21)×108/kg and 2.3(1.6 `6.3)×106/kg respectively. All patients achieved hemopoietc recovery. The median time of the engraftment of neutrophil and platelet was 9.7(8 `14) days and 12.9(9 `20) days posttransplant respectively. The incidence and severity of regimen-related toxicity were mild. The incidence of treatment related mortality (TRM)is 0%. The median follow-up of surviving patients was 31 months(range, 2 `86). Until now 46 patients are still alive, including 4 relapse cases. 13 cases were died of relapse. The five-year overall survival(OS) and the leukemia-free survival(LFS) were 77.3% and 71.9% respectively. The incidence of relapse was 23.2%. The OS and LFS in the low /moderate risk and high risk AL cohorts were 85.7%versus 40% and 79%versus 40% respectively(P<0.01) Conclusion AHSCT is the first option for the AL patients who were in good or moderate risk group and had achieved first complete remission. Regular consolidation chemotherapy after transplantation was beneficial to improve the LFS of AL patients.

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Outcome of HLA-matched related allogeneic hematopoietic stem cell transplantation for patients with acute leukemia in first complete remission treated in Eastern European centers. Better results in recent years

Annals of Hematology ◽

10.1007/s00277-009-0719-5 ◽

2009 ◽

Vol 88 (10) ◽

pp. 1005-1013 ◽

Cited By ~ 17

Author(s):

Sebastian Giebel ◽

Myriam Labopin ◽

Jerzy Holowiecki ◽

Boris Labar ◽

Mieczyslaw Komarnicki ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Acute Leukemia ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Eastern European ◽

Hematopoietic Stem ◽

First Complete Remission

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Posttransplant Cyclophosphamide-Based Haploidentical Vs Matched Unrelated Donor Peripheral Blood Hematopoietic Stem Cell Transplantation Using Myeloablative Targeted Busulfan-Based Conditioning for Pediatric Acute Leukemia

Blood ◽

10.1182/blood-2021-150547 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2874-2874

Author(s):

Kyung Taek Hong ◽

Hyun Jin Park ◽

Bo Kyung Kim ◽

Hong Yul An ◽

Jung Yoon Choi ◽

...

Keyword(s):

Stem Cell ◽

Acute Leukemia ◽

Board Of Directors ◽

Research Funding ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Matched Unrelated Donor ◽

Myeloablative Conditioning ◽

Advisory Committees ◽

Hematopoietic Stem

Abstract Haploidentical related donor (HRD) is a common alternative donor strategy used when matched sibling or unrelated donors are not available for hematopoietic stem cell transplantation (HSCT). Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis is an attractive option when performing a HRD HSCT because of its promising outcomes and easy application. However, there have been no studies comparing HRD HSCT with PTCy and MUD HSCT with antithymocyte globulin, using similar busulfan-based myeloablative conditioning regimen in pediatric acute leukemia. Herein, we compared the outcomes in children and adolescents with acute leukemia after HRD HSCT with PTCy (n=35) and matched unrelated donor (MUD) HSCT (n=45) after targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic monitoring. The median follow-up times of the HRD and MUD groups were 3.7 and 4.6 years. No engraftment failure was observed. The cumulative incidence of GVHD grades II-IV (34.3% versus 48.9%, p=0.142), grades III-IV (2.9% vs. 8.9%, p=0.272), extensive chronic GVHD (11.4% vs. 18.3%, p=0.417), relapse (25.6% vs. 28.0%, p=0.832), and non-relapse mortality (0% vs. 2.2%, p=0.420) were not significantly different. The 3-year severe chronic GVHD-free/relapse-free, leukemia-free and overall survival rates in the HRD and MUD groups were 62.9±8.7% versus 49.8±7.6% (p=0.318), 74.4±8.0% versus 67.5±7.2% (p=0.585), and 88.6±5.4% versus 83.7±5.7% (p=0.968), respectively. In subgroup analyses of patients with acute lymphoblastic leukemia and acute myeloid leukemia, there were no significant differences in outcomes between the groups. Our results demonstrated that HRD HSCT with PTCy using a targeted busulfan-based myeloablative conditioning shows outcomes similar to those of MUD HSCT. HRD HSCT with PTCy could be considered for pediatric acute leukemia patients who lack an HLA-matched donor. Disclosures Kang: Cartexell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Korea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen Korea: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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