scholarly journals Unrelated donor α/β T-cell and B-cell-depleted HSCT for the treatment of pediatric acute leukemia

2021 ◽  
Author(s):  
Allison Barz Leahy ◽  
Yimei Li ◽  
Julie-An Talano ◽  
Caitlin W Elgarten ◽  
Alix E. Seif ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Residual Disease ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Pediatric Transplantation ◽  
Increased Risk

Unrelated donor (URD) hematopoietic stem cell transplant (HSCT) is associated with an increased risk of severe GVHD. TCRαβ/CD19 depletion may reduce this risk, while maintaining graft-versus-leukemia. Outcome data with TCRαβ/CD19 depletion generally describes haploidentical donors, with relatively few URDs. We hypothesized that TCRαβ/CD19-depletion would attenuate the risks of GVHD and relapse for URD HSCT. Sixty pediatric and young adult (YA) patients with hematologic malignancies who lacked a matched-related donor were enrolled at two large pediatric transplantation centers between 10/2014 and 09/2019. All patients with acute leukemia had minimal residual disease testing and DP typing was available for 77%. All patients received myeloablative TBI- or busulfan-based conditioning with no post-transplant immune suppression. Engraftment occurred in 98%. Four-year overall survival was 69% (95%CI 52-81%) and leukemia-free survival was 64% (95%CI 48-76%), with no difference between lymphoid and myeloid malignancies (p=0.6297 and p=0.5441, respectively). One patient (1.7%) experienced primary graft failure. Relapse occurred in 11 patients (3-year cumulative incidence 21%, 95%CI 11-34), and 8 patients (cumulative incidence 15%, 95%CI 6.7-26) experienced non-relapse mortality. Grade III-IV acute GVHD was seen in 8 patients (13%), and 14 patients (26%) developed chronic GVHD, of which 6 (11%) had extensive disease. Non-permissive DP mismatch was associated with higher likelihood of acute GVHD (OR 16.50, 95%CI 1.67-163.42, p=0.0166), but not with the development of chronic GVHD. URD TCRαβ/CD19-depleted peripheral HSCT is a safe and effective approach to transplantation for children/YAs with leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02323867.

scholarly journals Low Dose Antithymocyte Globulin (ATG) for Graft-Versus-Host Disease (GVHD) Prophylaxis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5788-5788 ◽  
Author(s):  
Anand Tandra ◽  
Leland Metheny ◽  
David Yao ◽  
Paolo F. Caimi ◽  
Lauren Brister ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Lymphoproliferative Disorder ◽  
Low Dose ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hla Typing ◽  
Viral Reactivation ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis

Abstract ATG appears to reduce the incidence of acute and chronic GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Potential risks of this strategy include viral reactivation, delayed immune recovery and increased relapse rates. The ideal dosing of rabbit ATG in this context is largely unknown. We therefore hypothesized that low dose ATG would reduce the incidence of acute and chronic GVHD in matched unrelated donor (MUD) transplants without compromising survival and relapse rate. A retrospective analysis was performed of a cohort of high-risk MUD HSCT recipients treated since year 2013, when our practice changed to include rabbit ATG at 3 mg/Kg for all MUD transplants at the Case Medical Center in Cleveland, Ohio. Herein we present the results of this analysis. Methods. 58 MUD transplants were performed between years 2013 and 2016, with a median follow up of 262 days post-transplant. All donor-recipient pairs were matched by high resolution HLA typing at HLA-A, -B, -C, and DRB1, (8/8 matches) with the exception of 4 pairs (7/8 matches. Median age was 56 years (range, 53-64). Underlying diagnoses were AML (n=26), MDS (13), CML (n=5), NHL (n=9), Hodgkin's lymphoma (n=2), Multiple Myeloma (n=1) and myeloproliferative disorders (n=2). Preparative regimens were ablative in 26 cases (45 %) and of reduced intensity in 31 cases (55 %). Graft source was bone marrow (n=5) and peripheral blood (n=53). All but 4 pts received GVHD prophylaxis with tacrolimus, and mini-methotrexate (5 mg/m2 on days +1, +3, +6 and +11), in addition to rabbit ATG 3 mg/Kg divided in two doses on days -2 and -1 pre HSCT. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Human Herpes Virus (HHV6) PCR were conducted thrice weekly during the first 100 days after HSCT. Results. The 100-day cumulative incidence of grade II-IV acute GVHD was 41% (95% CI: 29-57; Fig 1), while the cumulative incidence of grade III-IV acute GVHD was 18% (95% CI: 9-35; Fig 2). 1-year cumulative incidence of chronic GVHD was 27% (95% CI: 17-42; Fig 3). At 180 days, the incidence of CMV viremia (defined as more than 1,000 copies/mL) was 25% (95% CI: 16-40), while the incidence of EBV and of HHV6 viremia was 35% (95% CI: 24-51) and 14% (95% CI: 8-27), respectively. There was no instance of EBV-related lymphoproliferative disorder. 3-year overall survival estimate is 48% (95% CI: 34-62). Cumulative incidence of Non-relapse mortality (NRM) and relapse at 1 year was 21% (95% CI: 12-37) and 44% (95% CI: 29-65), respectively. Conclusion. Our study shows that low dose rabbit ATG appears to reduce chronic GVHD rates without a major effect on acute GVHD incidence. CMV, EBV and HHV6 reactivation did occur, albeit at rates that are somewhat lower than those historically reported, without EBV-driven lymphoproliferative disorder. Disclosures Caimi: Genentech: Speakers Bureau; Roche: Research Funding; Novartis: Consultancy; Gilead: Consultancy.

Use Of Unrelated Donors In Elderly Patients (age >60 years) Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation For Hematologic Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5544-5544
Author(s):  
El-Cheikh Jean ◽  
Devillier Raynier ◽  
Fürst Sabine ◽  
Crocchiolo Roberto ◽  
Granata Angela ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Objectives The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens have allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. However, there are only limited data on the feasibility and outcomes of URD HCT in elderly patients.The aim of the study was to compare the outcome in OS and PFS for patients transplanted using unrelated donor (URD) in patients age 60 or older. Patients and methods We retrospectively analyzed outcomes in 62 consecutive hematologic malignancy patients aged > or =60 years (median, 62 years; range: 60-70 years) undergoing reduced intensity conditioning regimens (RIC) from URD. In this study, URD was used only when a MRD was not available. Then we compared the outcome of 17 elderly patients (age >65 years) with 44 younger patients aged between 60 and 65 years. Patient, disease and transplant characteristics are shown in Table 1. Results No patients experienced graft rejection. The median HCT comorbidity index score was 2 (range, 0 to 6). With a median follow up of 36 months (range, 5-74), the cumulative incidence of grades II to IV acute GVHD was 28% and of grades III to IV acute GVHD, 13%. At 2 years, the cumulative incidence of chronic GVHD was 27%, progression-free survival (PFS) was 62%, overall survival (OS) was 63%, and relapse was 14%. Non relapse mortality (NRM) was 24% at 2 years. The cumulative incidence of grade II–IV Acute GVHD was 43% for the younger group and 17% for the older group (P = 0.056). The cumulative incidence of chronic GVHD was not different between the two groups (23% vs. 45% (p=0.3), respectively). Two-year OS and PFS was 57% versus 86% (P = 0.059) and 55% versus 86% (P = 0.03), in the younger and the older group respectively. The 2-year NRM and relapse was 26% versus 14% (P = 0.4) and 19% versus 0% (P = 0.04), in the younger and older group respectively. Conclusions This retrospective study suggest that RIC HCT from URD is a safe and effective option for patients aged > or =60 years or older, and in the absence of suitable related donors, well-matched URD may offer a very reasonable alternative, and that does not appear to be associated with a detrimental outcome. However these results are encouraging showing once again that with an adequate selection, age is not a definitive limitation. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation for Children with Advanced Primary MDS: Results from the EWOG-MDS Study Group Employing a Pre-Transplant Preparative Regimen with Busulfan, Cyclophosphamide and Melphalan.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2300-2300 ◽  
Author(s):  
Charlotte Marie Niemeyer ◽  
Marco Zecca ◽  
Elisabeth Korthoff ◽  
Ulrich Duffner ◽  
Felix Zintl ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Observation Time ◽  
Unrelated Donor ◽  
Costal Margin ◽  
Intensive Chemotherapy ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Increased Risk

Abstract MDS in children is a rare disorder characterized by dysplasia and defined genetic abnormalities. In most patients (pts) MDS arises without known predisposing conditions (primary MDS). Here, we report the results of 55 males and 30 females with advanced primary MDS enrolled in the prospective EWOG-MDS trial 97. Data were analysed according to the most advanced FAB-type prior to SCT: 32 pts were classified as RAEB, 40 as RAEB-t and 13 as myelodysplasia-related AML (MDR-AML). Median age at diagnosis was 9.5 yrs (0.1–17.6) and median time from diagnosis of advanced MDS to SCT 4 mo (0.5–31). Cytogenetics revealed monosomy 7 in 32 pts, trisomy 8 in 7, a complex karyotype in 9 and other abnormalities in 9; karyotype was normal in 26 pts and unknown in 2. 31 pts had received AML-like therapy prior to SCT. All pts were given an unmanipulated graft after condititioning with busulfan 16 mg/kg, cyclophosphamide 120 mg/kg and melphalan 140 mg/m. Source of stem cells was bone marrow in 56 pts, peripheral blood in 25, cord blood in 2 and unknown in 2. 36 pts were transplanted from an HLA-identical relative (MFD), 49 pts from an HLA-identical or 1-antigen disparate unrelated donor (UD). GVHD prophylaxis consisted of CSA alone for MFD, whereas recipients of a UD graft generally received CSA, methotrexate and anti-lymphocyte globulin. Two pts suffered graft failure. The cumulative incidence of grade II-IV acute GVHD and chronic GVHD was 40% (SE 5%) and 25% (SE 5%), respectively. 18 pts suffered transplant-related mortality (TRM), the cumulative incidence of TRM in pts grafted from a MFD or UD being 14 and 25%, respectively (p=n.s.). Presence of acute GVHD II-IV (p<0.01), spleen size at SCT ≥ 1 cm below the costal margin (p=0.03) and age ≥ 12 years (p=0.04) predicted an increased risk of TRM. 17 patients relapsed at a median of 12 mo after SCT (1–107). The 5-year probability of leukemia recurrence was 29%, with no difference between MFD and UD transplants. While the highest FAB type prior to SCT predicted relapse with a cumulative incidence rate increasing from RAEB (13%, SE 10%) to RAEB-t (24%, SE 11%) and MDR-AML (69%, SE 20%) (p=0.03), the use of intensive chemotherapy prior to SCT or blast percentage at SCT did not. With a median observation time after SCT of 29 months (6–107) the EFS at 5-years was 62% (SE 12%) and 39% (SE 11%) for pts given SCT from a MFD or an UD, respectively (p=n.s). These results indicate that a large proportion of pts with advanced MDS can be rescued by SCT. Disease recurrence remains the main cause of treatment failure. Intensive chemotherapy prior to SCT should not be routinely employed.

Characteristics and Outcome of Therapy-Related MDS Developing after Primary Cancer in Children.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2514-2514
Author(s):  
R. Ammann ◽  
M. Zecca ◽  
D. Betts ◽  
J. Harbott ◽  
M. Trebo ◽  
...  
Keyword(s):  
Median Time ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Platinum Compounds ◽  
Hematopoietic Stem ◽  
Monosomy 7 ◽  
Prior Therapy ◽  
Increased Risk ◽  
Preparative Regimen

Abstract Treatment-related myelodysplastic syndrome (tMDS) is a serious complication of therapy of childhood cancer. Here we report on 59 patients (pts) (35 males, 24 females) with tMDS enrolled in the prospective study EWOG-MDS 98. Prior malignancy was ALL in 21 pts, AML in 5, lymphoma in 6, CNS tumors in 12, and other solid tumors in 15. Median age at diagnosis of tMDS was 11.2 yrs (range 1.2 – 23.2), and median time between first malignancy and tMDS 3.3 yrs (range 0.5 – 11.1). Disease was classified as refractory cytopenia in 15 pts, RAEB in 30 and RAEB-T in 14. Of the 47 pts with cytogenetic analysis at diagnosis, 77% had an abnormal karyotype, including 38% that were complex. Monosomy 7 with or without other abnormalities was detected in 38%. Progression of disease was noted in 26 of 52 evaluable pts at a median time of 2.5 mo (range 0.3 – 16) from diagnosis; the cumulative incidence of progression being 74%. After a median follow-up time of 20 mo (range 3–69) 28 pts are alive with an estimated 5-year overall survival of 32% (95% CI 20 – 51). No child survived beyond 15 mo from diagnosis without receiving allogeneic hematopoietic stem cell transplantation (HSCT). HSCT was performed in 45 pts. Source of stem cells was bone marrow in 24 pts, peripheral blood in 20 and cord blood in 1. The donor was an HLA-identical relative (MFD) in 18 cases, while 26 pts were transplanted from an HLA-matched or 1-antigen/allele disparate unrelated donor (UD) and 1 pt from a 2-antigen disparate parent. Preparative regimen included busulfan 16 mg/kg, cyclophosphamide 120 mg/kg and melphalan 140 mg/m2 in 32 pts. Prophylaxis of GVHD generally consisted of cyclosporine-A for MFD, combined with methotrexate and ALG for UD. Two patients had graft failure. The cumulative incidence of grade II–IV acute GVHD and chronic GVHD were 32% (95% CI 28 – 37) and 24% (95% CI 19 – 28), respectively. Twelve pts suffered transplant-related mortality (TRM), the cumulative incidence of TRM in pts transplanted from a MFD or UD being 12% and 39%, respectively (P=0.058). Prior therapy with platinum compounds was an independent predictor of an increased risk of TRM. Fifteen pts relapsed at a median time of 9 mo (range 2 – 29) after HSCT, the 5-year cumulative incidence of relapse being 44% (95% CI 21 – 66). A WBC &gt; 4 G/L at diagnosis predicted a higher risk of relapse. Twenty-one of the 45 pts transplanted are alive and 19 are disease-free. The estimated 5-year EFS after HSCT was 27% (95% CI 15 – 47). Prior therapy with platinum compounds, a WBC &gt; 4 G/L at diagnosis, and a female donor predicted inferior EFS, while HSCT from an UD versus MFD resulted in similar outcome (5-year EFS, 21% and 39%, respectively). AML-type therapy prior to HSCT did not improve survival. Innovative stragegies for improving the outcome of these patients are warranted.

Adenovirus Infections in Patients Undergoing Umbilical Cord Blood Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1132-1132
Author(s):  
Gabriela Soriano ◽  
Vincent T Ho ◽  
Karen K Ballen ◽  
Philippe Armand ◽  
Corey Cutler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Adenovirus Infection ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Increased Risk

Abstract Abstract 1132 Poster Board I-154 Background Adenovirus infections are an important source of morbidity and mortality among stem cell transplant (SCT) recipients, with infections occurring in 5-21% of patients, with an associated mortality of up to 50%. Little is known about the clinical features and incidence of adenovirus infection after cord blood SCT (CB-SCT) in adults. Methods The DFCI/BWH umbilical CB-SCT cohort transplanted from 2003-2008 was analyzed. Adenovirus infection was diagnosed by blood PCR, culture, immunofluorescence, or immunohistochemistry. Baseline covariates included age, sex, malignancy being treated, conditioning, graft versus host disease (GVHD) prophylaxis, incident GVHD and its severity. Data was censored on 7/1/2009. Results 92 patients underwent CB-SCT during the period; 89 were double cord recipients. 68 underwent reduced-intensity conditioning consisting of fludarabine (180mg/m2), melphalan (100 mg/m2), and ATG (Thymoglobulin® 6 mg/kg). GVHD prophylaxis with sirolimus and tacrolimus was used in 57 patients, cyclosporine and mycophenolate mofetil in 17, and other combinations in the rest of the cohort. Median follow up was 363 days (range, 1-1848 days). Adenovirus testing was routinely done for persistent febrile illness, respiratory, gastrointestinal and hepatic syndromes. Adenovirus infection was diagnosed in 6/92 for a cumulative incidence of 6.5%. Three were female, median age was 51 years (range, 37-62). Underlying disease was MDS in 1, NHL in 2, AML in 2 and HD in 1. Median time to diagnosis was 152 days (range, 23-768) from CB-SCT. Three patients were diagnosed within 100 days post CB-SCT: all had diarrhea and fever. The other 3 patients were diagnosed between 8 months to 2 years after transplant: one patient each had respiratory, urinary and gastrointestinal infection. Three of the six patients developed concomitant CMV reactivation with their adenovirus infection: 2 of these occurred within 100 days of transplant, and one occurred 1 year after HSCT. Three of the 6 patients with adenovirus infection also developed grade II-IV acute GVHD and 2 developed chronic GHVD. The onset of acute GVHD was closely associated in time with the development of adenovirus infection; this was not the case of chronic GVHD. Two patients had blood adenovirus loads > 1 million copies/mL, and were treated with cidofovir with improvement in symptoms and decline in virus loads. Of the 6 patients, 3 died of relapsed disease, none died of complications attributable to adenovirus infection. Conclusions Since recipients of T-cell depleted transplants are at higher risk for viral infections compared to those receiving unmanipulated grafts, we hypothesized that umbilical cord recipients would be at an increased risk for adenovirus infection due to the limited number of immunocompetent T-cells in cord blood grafts. Surprisingly, we detected adenovirus infection in only 6.5% of patients in this cohort, and none died as a consequence of adenovirus infection. Further study of the immunity to adenoviruses in CB-SCT adult recipients is warranted. Disclosures Off Label Use: cidofovir for treatment of adenovirus infection.

scholarly journals Long-Term Follow-up of Hematopoietic Stem Cell Transplantation with the Modified Peking Regimen for the Treatment of Acute Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2034-2034
Author(s):  
Xi Yang ◽  
Chenglong Li ◽  
Rong Zhang ◽  
Hong Zheng ◽  
Qing Wei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Free Survival

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment strategy for patients with acute leukemia. The ATG-based transplantation system initiated by Peking University people's hospital, known as the Peking regimen, has become a mainstream transplant system worldwide. Here, based on the Peking regimen, we report a modified protocol:(1)add Fludarabine and replace ATG with ATG-F in the conditioning regimen; (2)transfuse higher-dose cell collections from granulocyte-colony stimulating factor(G-CSF) primed bone marrow and peripheral blood samples; (3) add Basiliximab (a CD25-antibody) on day +3 for acute GVHD prophylaxis. In this study, 265 patients (158 patients with haplo-SCT and 107 patients with sibling-SCT) underwent allo-HSCT with our modified protocols. All patients achieved sustained full-donor chimerism. The incidence of grade II-IV and III-IV acute GVHD in haplo-SCT comparing with sibling-SCT was 36.1%(57/158) vs 17.8%(19/107)(P=0.001) and 13.3% (21/158) vs 9.3%(10/107)(P>0.05) respectively. The 2-year cumulative incidence of total chronic GVHD and extensive chronic GVHD in haplo-SCT was 41% (65/158) and 15% (24/158) respectively. The 3-year cumulative incidence of non-relapse mortality (NRM) in haplo-SCT and sibling-SCT was 6.3% (10/158) and 4.7%(5/107) respectively(P>0.05). The 100-day cumulative incidence of CMV viremia in haplo-SCT and sibling-SCT was 35.5% (56/158) and 23.4%(25/107) respectively(P=0.036). A total of 36 patients in haplo-SCT group and 24 patients in haplo-SCT group had recurrent disease, reaching a cumulative incidence of relapse of 20.8% in haplo-SCT and 23.4% in sibling-SCT at 3 years respectively(P>0.05). The relapse ratio of haplo-SCT and sibing-SCT in the 1st year, between the 1st and the 2nd year and after 2 years was 21.5% vs 14.1%(P>0.05), 1.3%(2/158) vs 0%(P>0.05) and 0% vs 6.5%(P=0.009) respectively. The 3-year overall survival(OS) and leukemia-free survival(LFS) rates in haplo-SCT and sibling-SCT was 78.8% vs 74.2% and 76.8% vs 75.04% respectively(P>0.05) by the Kaplan-Meier estimate. The 3-year GVHD-free and leukemia-free survival rates (GRFS) in haplo-SCT and sibling-SCT were 43.4% vs 69.5%(P=0.045) respectively. Lower OS in haplo-SCT was associated with III-IV aucte GVHD and lower MNC(<19×10^8/L) in grafts by Cox regression analysis. In a word, the results from our experience showed that the modified protocol based on the Peking Regimen is safe and reliable for acute leukemia patients and brings on a long-stage survival post transplantation. Disclosures Zheng: Pfizer: Research Funding.

scholarly journals Unrelated donor vs HLA-haploidentical α/β T-cell– and B-cell–depleted HSCT in children with acute leukemia

Blood ◽  
2018 ◽  
Vol 132 (24) ◽  
pp. 2594-2607 ◽  
Author(s):  
Alice Bertaina ◽  
Marco Zecca ◽  
Barbara Buldini ◽  
Nicoletta Sacchi ◽  
Mattia Algeri ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Leukemia ◽  
B Cell ◽  
Cumulative Incidence ◽  
Therapeutic Option ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Probability Of Survival

Abstract Traditionally, hematopoietic stem cell transplantation (HSCT) from both HLA-matched related and unrelated donors (UD) has been used for treating children with acute leukemia (AL) in need of an allograft. Recently, HLA-haploidentical HSCT after αβ T-cell/B-cell depletion (αβhaplo-HSCT) was shown to be effective in single-center studies. Here, we report the first multicenter retrospective analysis of 127 matched UD (MUD), 118 mismatched UD (MMUD), and 98 αβhaplo-HSCT recipients, transplanted between 2010 and 2015, in 13 Italian centers. All these AL children were transplanted in morphological remission after a myeloablative conditioning regimen. Graft failure occurred in 2% each of UD-HSCT and αβhaplo-HSCT groups. In MUD vs MMUD-HSCT recipients, the cumulative incidence of grade II to IV and grade III to IV acute graft-versus-host disease (GVHD) was 35% vs 44% and 6% vs 18%, respectively, compared with 16% and 0% in αβhaplo-HSCT recipients (P &lt; .001). Children treated with αβhaplo-HSCT also had a significantly lower incidence of overall and extensive chronic GVHD (P &lt; .01). Eight (6%) MUD, 32 (28%) MMUD, and 9 (9%) αβhaplo-HSCT patients died of transplant-related complications. With a median follow-up of 3.3 years, the 5-year probability of leukemia-free survival in the 3 groups was 67%, 55%, and 62%, respectively. In the 3 groups, chronic GVHD-free/relapse-free (GRFS) probability of survival was 61%, 34%, and 58%, respectively (P &lt; .001). When compared with patients given MMUD-HSCT, αβhaplo-HSCT recipients had a lower cumulative incidence of nonrelapse mortality and a better GRFS (P &lt; .001). These data indicate that αβhaplo-HSCT is a suitable therapeutic option for children with AL in need of transplantation, especially when an allele-matched UD is not available.

scholarly journals Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 53-66
Author(s):  
Vaneuza A. M. Funke ◽  
Maria Claudia Rodrigues Moreira ◽  
Afonso Celso Vigorito
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

scholarly journals Family Mismatched Donor Transplantation for Myelofibrosis: A Retrospective Analysis of the EBMT Chronic Leukaemia Working Party

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4655-4655 ◽  
Author(s):  
Kavita Raj ◽  
Eduardo Olavarria ◽  
Diderik-Jan Eikema ◽  
Liesbeth C de Wreede ◽  
Linda Koster ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Mismatched Donor

Abstract Background: Allogeneic stem cell transplantation is a treatment option for patients with advanced myelofibrosis. Problems encountered include an increased risk of delayed or poor engraftment and in the mismatched unrelated donor setting a higher rate of GVHD and particularly poor outcomes. As for other indications for allogeneic stem cell transplants, patients for whom either a matched sibling or matched unrelated donor is not available are considered for either a double umbilical cord blood, a mismatched unrelated donor or haploidentical stem cell transplant. Data on the latter option are limited and we reviewed registry data on all family mismatched donor transplants performed between 2001 and 2015 and reported to the EBMT registry. Results: Records retrieved 69 patients with myelofibrosis transplanted between November 2001 and November 2015. 44 (64%) were male. 50 (74%) had primary myelofibrosis,18 (27%) had secondary myelofibrosis (6 from ET, 5 from PRV and 7 others) and unknown 1(2%). Of 25 patients for whom the JAK2 V617F mutation status was known, 15 (22%) harboured the mutation. Patient Karnofsky performance status was > 70% in 98%. Of the mismatched family donors, 47 (68%) were male and 22 (31%) female. Donors were HLA mismatched at 1 locus in 12 (17%) and 2 or more loci in 48 (69%). Donor-recipient serology combinations were CMV -/- in 8 (12%), +/- in 4 (6%), -/+ in 15 (22%) and +/+ in 34 (49%) missing 8 (12%). Bone marrow was the stem cell source in 34 (49%) and peripheral blood in 35 (51%). The median total nucleated cell count (TNC) infused was 7.5x108/kg (range 2.3-21x108/kg) from data available in 17 patients. The median CD34+ cell dose was 6.9x106/kg (range 1.9-18.18x106/kg) from data available in 19 patients. Conditioning was myeloablative in 48 (70%) and RIC in 21 (30%) The conditioning regimes were varied but the predominant ones were Fludarabine, Busulphan, ATG (FBATG) and Thiotepa, Busulphan, Fludarabine (TBF). TBI was administered in 8 (12%) and in vivo T cell depletion in 22 (32%), ex-vivo T cell depletion in 5 (7%) patients. GVHD prophylaxis varied with post transplant Cyclophosphamide administered in 34/67 (49%) and ATG in 19/67 patients (28%). Neutrophil engraftment was established in 53 (82%) at a median of 20 days (range 11-83). Primary graft failure occurred in 8 (12%) and secondary graft failure in 4 (6%). This occurred at a median of 12 months (range 4.5-35 months). Eleven of these patients had a second allograft at a mean interval of 6.4 months. Responses to the first allograft (censoring for patients who had a second allograft) with data available in 45 patients, showed that complete remission was achieved in 35 patients (78%), 6 (13%) were never in CR and 4 (9%) were not evaluable. The cumulative incidence of grade II-IV acute GvHD at 100 days was 12% (95% CI 4-21%) and for grade III-IV acute GvHD at 100 days it was 5% (95% CI 3-11%). Data for chronic GVHD was valid in 49 patients. The cumulative incidence of chronic GvHD at 2 years was 62% (95% CI 47-76%). The cumulative incidence of limited cGvHD was 45% (95% CI 31-59%) whereas the cumulative incidence of extensive cGvHD was 10% (95% CI 2-19%). The median follow up was 24 months (95% CI 13-35 months). The 2-year OS was 51% (95% CI 37-76%) and the 5-year OS was 38% (95% CI 21-55%). The 2-year RFS was 44% (95% CI 30-59%) and the 5-year RFS was 31% (95% CI 15-48%). The 2 year cumulative incidence of relapse was 14% (95% CI 5-24%). The 2 year NRM was 41% (95% CI 28-55%), which increased to 54% (95% CI 37-72%) at 5 years. The main causes of death were infection (16, 24%), GVHD (7, 10%) organ damage or failure (3, 5%), relapse/disease progression (1, 2%) and secondary malignancy or PTLD (1, 2%). On univariate analysis there was no significant effect of recipient gender, donor gender, degree of HLA mismatch 1 vs >1 Ag MM, CMV matching between donor and recipient, primary or secondary MF, disease stage at transplant (chronic versus advanced phase), conditioning intensity, conditioning regimen, GVHD prophylaxis with ATG or post transplant cyclophosphamide or stem cell source on overall survival. Conclusion: Concerns regarding engraftment and secondary graft failure have excluded patients with myelofibrosis from clinical trials of mismatched related donor transplant. The data suggest that engraftment is feasible, and PFS and OS can be attained with limited severe chronic GVHD with family mismatched donors in this setting. Disclosures Ciceri: MolMed SpA: Consultancy.

scholarly journals RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Dânia Sofia Marques ◽  
Carlos Pinho Vaz ◽  
Rosa Branca ◽  
Fernando Campilho ◽  
Catarina Lamelas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Increased Risk

Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due toRhizomucor sp.and rhinoencephalitis due toScedosporium apiospermum6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis), its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies).

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