PTCy-based Haploidentical vs Matched Unrelated Donor Peripheral Blood HSCT Using Myeloablative Targeted Busulfan-based Conditioning for Pediatric Acute Leukemia

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.

Download Full-text

Post-Transplant Cyclophosphamide for Gvhd Prophylaxis in Matched Unrelated Donor Transplantation Compared to ATG-Based Prophylaxis

Blood ◽

10.1182/blood-2019-124849 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3285-3285

Author(s):

Rebeca Bailén ◽

Mi Kwon ◽

Maria Jesus Pascual-Cascon ◽

Anna Torrent ◽

Christelle M Ferra ◽

...

Keyword(s):

Peripheral Blood ◽

Cumulative Incidence ◽

High Dose ◽

Unrelated Donor ◽

Matched Unrelated Donor ◽

Hematopoietic Stem ◽

Free Survival ◽

Post Transplant ◽

Gvhd Prophylaxis

Background: Post-transplant high dose cyclophosphamide (PT-CY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT). The use of PT-CY in HLA-identical donor is less explored. In this study, we analyzed the results of PT-CY for GVHD prophylaxis in matched unrelated donor (MUD) HSCT and compared them with those obtained after prophylaxis with anti-thymocyte globulin (ATG), methotrexate (MTX) and cyclosporine (CsA). Methods: 132 matched unrelated donor HSCT from 4 Spanish centers have been analyzed: 60 performed between 2010 and 2018 using ATG-MTX-CsA and 72 performed between 2014 and 2018 using PT-CY. Results: Baseline characteristics and post-transplant complications are shown in Table 1. Peripheral blood was used as graft source in 92% of the patients in the ATG group and in 78% in the PT-CY group. GVHD prophylaxis consisted in rabbit ATG either 2mg/kg days -4 to -2 (41 patients, 68%) or 0.5mg/m2 on day -3 followed by 1mg/kg days -2 and -3 (19 patients, 32%), MTX days +1, +3, +6 and +11, and CsA from day -1 in the ATG group. The PT-CY group received cyclophosphamide 50 mg/kg/d on days +3 and +4, followed by either CsA or tacrolimus plus mycophenolate mofetil (MMF) from day +5 in 30 patients (42%), or cyclophosphamide on days +3 and +5 combined with CsA or tacrolimus in 42 patients (58%; 16 out of them also received sirolimus due to 9/10 HLA-match). Cumulative incidence of grade II-IV (67% vs 46%, p=0.008) and III-IV (34% vs 3%, p=0.003) acute GVHD, were significantly higher in the ATG group (Figure 1). There were no differences in the 2-year cumulative incidence of chronic moderate to severe GVHD (23% vs 24%, p=0.86). After a median follow-up of 78 months for the ATG group and 26 months for the PT-CY group, no differences were found in the 2-year overall survival (58% vs 60%, p=0.475), 2-year event-free survival (51% vs 50%, p=0.961) and the composite endpoint of GVHD-free and relapse-free survival (44% vs 40%, p=0.742). The 2-year cumulative incidence of relapse (22% vs 26%, p=0.67) and non-relapse mortality (NRM) (24% vs 22%, p=0.68) were also similar between both groups. However, NRM in the ATG group was due to GVHD in 9 out of 16 patients, while in the PT-CY group NRM was mostly due to infections and organ toxicity and only 3 out of 15 patients died due to GVHD. The incidence of sinusoidal obstruction syndrome was low in both groups (0% vs 4%, p=0.11). CMV reactivation rates were similar (40% vs 51%, p=0.191). However, both hemorrhagic cystitis and EBV reactivation were higher in the ATG group (56% vs 12%, p=0.00, and 5% vs 0%, p=0.05, respectively). Conclusions: In our experience, GVHD prophylaxis using PT-CY combined with additional immunosuppression after MUD HSCT, using mostly peripheral blood as graft source, resulted in lower incidence of aGVHD compared to prophylaxis based on ATG-MTX-CsA. Although no impact on non-relapse mortality was observed, GVHD associated mortality was higher in the ATG group as well as cystitis and EBV reactivations. Prospective studies with longer follow-up are needed to confirm these observations. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Decision Analysis of Donor Selection in Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia in First Remission-Related Donor with HLA-1 Antigen Mismatch in the GVH Direction vs. HLA-8/8 Allele-Matched Unrelated Donor

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2012.11.534 ◽

2013 ◽

Vol 19 (2) ◽

pp. S346-S347 ◽

Cited By ~ 1

Author(s):

Junya Kanda ◽

Akiyoshi Takami ◽

Junji Tanaka ◽

Koichi Miyamura ◽

Kazuteru Ohashi ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Acute Leukemia ◽

Decision Analysis ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Unrelated Donor ◽

Matched Unrelated Donor ◽

First Remission ◽

Related Donor

Download Full-text

Transplant CD34+ Cell Dose Affects Outcomes Following Allogeneic Peripheral Blood Stem Cell Transplantation from a Matched Unrelated Donor.

Blood ◽

10.1182/blood.v106.11.2056.2056 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2056-2056

Author(s):

Ryotaro Nakamura ◽

Joycelynne Palmer ◽

Roberto Rodriguez ◽

Pablo Parker ◽

David Senitzer ◽

...

Keyword(s):

Peripheral Blood ◽

Acute Gvhd ◽

Unrelated Donor ◽

Matched Unrelated Donor ◽

Relapse Risk ◽

Cell Dose ◽

Grade Ii ◽

Full Intensity ◽

The Impact ◽

Reduced Intensity

Abstract Peripheral blood stem cells (PBSC) have been increasingly used in the matched unrelated donor (MUD) transplant setting, but the impact of CD34 cell dose on outcomes following MUD-PBSC transplant have not been well characterized. Between 8/00-12/04, a total of 181 patients underwent MUD-PBSC transplantation at our institution under IRB-approved protocols. Patient’s age at transplant ranged from 1 to 67 years (median 44). Eighty-two were female and 99 were male. The cohort consisted of 68 patients with AML, 38 with ALL, 18 with CML, 18 with NHL, 17 with MDS, and the remaining 22 with other diagnosis (CLL, MM, MPD, etc.). Of 181 patients, 35 were considered to have low-risk disease (acute leukemias in CR1 or CML-CP). Patients were conditioned with either full-intensity regimen (TBI+Cy or VP16, or BuCy: n=83) or reduced-intensity regimen (fludarabine+melphalan or busulfan: n=98). GVHD prophylaxis consisted of tacrolimus+methotrexate for full-intensity transplants and cyclosporine+mycophenolate+/− methotrexate for reduced-intensity transplants. Median (range) CD34+ cell, lymphocyte (Ly), and mononuclear cell (MNC) doses were 6.7 (0.6–28) x106/kg, 440 (40–2640) x106/kg, and 710 (50–5060) x106/kg respectively. A strong correlation exists between Ly and MNC doses (r2=. 52, p<0.01), but not between CD34+ cell and Ly or MNC doses. The median time to ANC≥500/uL was 16 days (range: 7–52) and platelet≥20k/ul at 20 days (range: 12–98). After a median follow up of 18 months (range: 3–49), 103 patients are alive. The two-year overall survival (OS), disease-free survival (DFS), relapse, and transplant-related mortality (TRM) probabilities were 54%, 46%, 30%, and 31% respectively. Grade II–IV acute GVHD occurred in 64% of patients (grade 3–4: 31%). Chronic GVHD was observed in 64% of evaluable patients. By univariate analysis, a CD34+ cell dose ≥ 4.2x106/kg (the lowest quartile) was associated with significantly lower relapse risk (Hazard Ratio=0.4; p=0.02), and a trend for improved DFS (HR=0.6; p=0.06) and OS (HR=0.64; p=0.08). After adjusting for the patient’s age at transplant, disease risk classification, and conditioning regimen (full-intensity vs. reduced intensity), the impact of CD34+ cell dose (≥ 4.2x106/kg) remained significant for relapse (HR=0.4; p<0.01), DFS (HR=0.6; p=0.05), with a trend for OS (HR=0.6; p=0.07). CD34+ cell dose ≥6.7x106/kg (median) was associated with a trend for reduced relapse risk (HR= 0.5; p=0.06) without impact on DFS, OS, or TRM. A CD34+ cutoff at 9.5 x106/kg (the highest quartile) had no impact on OS, DFS, relapse, or TRM. There was no association between the CD34 cell dose and acute GVHD (grade II–IV or III–IV). In conclusion, within the range of CD34 doses in our study, the CD34+ cell dose ≥ 4.2x106/kg was associated with better transplant outcomes in MUD-PBSC transplants. We observed no adverse effect of receiving CD34+cell dose > 9.5 x106 (the highest quartile) in transplant outcomes including acute GVHD and TRM.

Download Full-text