Allogeneic Stem Cell Transplantation (allo-SCT) in 192 Acute Myeloid Leukemias (AML): A Single Center Experience From 1982 to 2010

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4498-4498
Author(s):  
Carmen Montes-Gaisan ◽  
Jorge Monge ◽  
Clara Martin ◽  
Zurie Diez ◽  
Johny Alberto Hinostroza ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
The Other ◽  
Univariable Analysis ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source

Abstract Abstract 4498 Background: Giving the fact that allo- SCT currently offers patients with high risk AML the best chance of cure, we`ve aimed to investigate the outcome of AML patients who have undergone allo-SCT in our center, considered as one of spanish reference hospital in SCT, and the parameters that have been able to influence in relapse rate (RR), overall survival (OS) and relapse free survival (RFS). Methods: Retrospective study in 192 AML patients who have undergone allo-SCT between 1982 and 2010. The analysis has been performed in 171 patients (85 male and 86 female) by excluding 21 acute promyelocitic leukemias (APL): 65 patients until 1999 and 106 since 2000. Median age was 37 1874 and median lecocyte count, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(13400/\hbox{ L }\frac{470}{250000}\) \end{document}. 82 were de novo AML and 87 were in morfologic complete remission (70 in first CR). 14 patients had received a previous SCT. Cytogenetic risk was as follows: 55 intermediate, 34 high and 11 low. Conditioning regimen was ablative in 162 patients: CyTBI (36), BuCy (31), BuFlu (30) and others (3). 130 patients (76) underwent a related allo-SCT (95 of them were matched) and 41 patients (24), an unrelated allo-SCT (64 of them were matched). Stem cell source was bone marrow (BM) in 146 patients (85) and only 3 patients received umbilical cord (UC). Graft versus host disease (GvHD) prophilaxis was based on Ciclosporine in 150 patients (88). Median time from last treatment was 73 days 12268. Results: The median follow-up of this study was 61 months 1317. OS at 1, 3 and 5 years were 57, 44 and 40. RFS at 1, 3 and 5 years were 62, 50 and 45. Early mortality (before day 100) was 26 (43 until 1999 and 15 since 2000, p0,0001): 18 patients because of infections, 10 because of toxicity, 9 because of disease and 7 because of EICH. Late mortality was 27 (more than the half because of relapse, with no significant difference between 19881999 and 20002010). Cumulative relapse incidence at 5 years was 35, with a median time of relapse of 4 months. Secondary malignancies incidence was 5. Multivariable analysis showed that Transplantation Related Mortality (TRM) was influenced by: year of allo-SCT (OS at 5 years of 49 if 20002010 vs 28 if 19821999, p0,0001), late engraftment (p0,002) and severe acute GvHD (OS at 5 years of 45 if no evidence/grade I-II vs 25 if grade III-IV, p0,071). The other important parameters which lost its univariable analysis significance were donor type, recipient age and conditioning regimen. No difference was found in case of HLA and ABO discordance or donor/recipient CMV status. Multivariable analysis also showed that RR and RFS at 5 years was influenced by: disease status at allo-SCT (50 if 1CR vs 0 if 2CR/PR/refractory disease, p0,002), chronic GvHD (67 if present vs 41 if absent, p0,035) and leucocyte count at diagnosis (54 if 20000/ L vs 37 if 20000/ L, p0,038). The other important parameters which lost its univariable analysis significance were cytogenetic risk, initial induction response and positive minimal residual disease (MRD) before allo-SCT. No diference was found in case of ethiologic classification or stem cell source. Conclusions: Allo-SCT is a curative procedure in AML patients (global RFS of 50 at 3 years), specially when disease is under control and patient develops chronic GvHD. In the last decade, there have been important improvements in the procedure which have led to a significant decrease in TRM, and consequently, a significant increase in OS. Disclosures: No relevant conflicts of interest to declare.

Influence of Stem Cell Source On GvH and NRM: Comparison of 10/10 HLA-Matched Unrelated Donor (MUD) with 9/10 HLA-Mismatched Unrelated Donor (MMUD) and Unrelated Cord Blood (UCB) Transplants.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3135-3135
Author(s):  
Clémence Granier ◽  
Emeline Masson ◽  
Lucie Biard ◽  
Raphael Porcher ◽  
Regis Peffault de la Tour ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source

Abstract Abstract 3135 Background: When an HLA-matched donor is not available for allogeneic Hematopoietic Stem Cell Transplantation (HSCT), the use of an alternative HLA-mismatched stem cell source may be considered. In Europe, HLA compatibility for HSCT is calculated for 10 alleles (HLA-A, -B, -C, -DRB1, -DQB1). The aim of this study was to retrospectively compare outcomes after transplantation from 10/10 HLA-MUD, 9/10 HLA-MMUD and UCB performed at the Hospital Saint Louis (Paris, Fr). Methods: Patients receiving a first allogeneic transplantation from a 10/10, 9/10 UD or UCB from 2000 to 2011 were included. High resolution HLA typing was performed by PCR SSO and SSP for HLA loci: A, B, C, DRB1 and DQB1. The following variables were studied as risk factors for transplant outcomes: disease, disease risk (standard/high risk), age at transplant, gender, donor/recipient sex-matching, ABO matching, donor/recipient CMV status, conditioning regimen, and use of anti-thymoglobulin (ATG). Results: 355 consecutive patients with hematologic malignancies were analyzed. One hundred and ninety-six were transplanted with MUD, 84 with MMUD (mismatches for HLA-A: 16%, -B: 16%, -C: 39%, -DRB1: 8%, -DQB1: 21%) and 75 with UCB (52% with single and 48% with two UCB unit; 87% of all UCB transplants were 4–6/6 HLA-matched). Median patient age was 31 (range: 5–55). Patient characteristics differed between the 3 groups: (i) median age at transplant: 36 in MUD, 31 in MMUD, 22 in UCB (p<0.0001), (ii) high risk disease: 37%, 51%, 68% (p<0.0001), (iii) CMV negative donor/positive recipient: 31%, 36%, 60% (p<0.0001), (iv) use of ATG: 37%, 64%, 55% (p<0.0001). Cumulative incidences of grade II-IV and grade III-IV acute GvHD disease (aGvHD) were 61% (66% for MUD, 60% for MMUD and 48% for UCB) and 17% (17%, 24% and 15%), respectively. Three-year cumulative incidence of chronic GvHD (cGvHD) was 46% (51% for MUD, 49% for MMUD and 29% for UCB). Three-year NRM was 34% (28% for MUD, 31% for MMUD and 51% for UCB). Graft failure occurred in 15% of UCB patient, 8% in MMUD group and 3% in MUD group (significant difference between UCB and MUD: OR=5.44, 95%CI 1.93–15.3, p=0.001). Multivariate analysis is summarized in table 1. It showed that MMUD tented to have a higher incidence of aGvHD III-IV than MUD and UCB. UCB had a lower incidence of cGvHD than MMUD. No significant effect of HSCT source on NRM was demonstrated. Conclusion: Compared to MMUD, UCB-HSCT induces less cGvHD and non significantly increased NRM. Compared to MUD, MMUD and UCB-HSCT did not result in a clear increase of NRM. UCB and 9/10 HLA-MMUD are both suitable stem cell sources for patients who cannot benefit from 10/10 HLA-MUD transplant. Disclosures: No relevant conflicts of interest to declare.

Autologous Stem Cell Transplantation (ASCT) in 121 Acute Myeloid Leukemias (AML): A Single Center Experience From 1988 to 2010

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3099-3099
Author(s):  
Carmen Montes-Gaisan ◽  
Amalia Cuesta ◽  
Susana Herraez ◽  
German Perez ◽  
Guillermo Martin ◽  
...  
Keyword(s):  
Stem Cell ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
Young Patients ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source ◽  
De Novo Aml

Abstract Abstract 3099 Background: Despite the fact that allogeneic SCT currently offers patients with high risk AML the best chance of cure, we've aimed to investigate the outcome of AML patients who have undergone ASCT in our center, considered as one of spanish reference hospital in SCT, and the parameters that have been able to influence in relapse rate (RR), overall survival (OS) and relapse free survival (RFS). Methods: Retrospective study in 121 AML patients who have undergone ASCT between 1988 and 2010. The analysis has been performed in 95 patients (50 male and 45 female) by excluding 26 acute promyelocitic leukemias (APL): 62 patients until 1999 and 33 since 2000. Median age was 45 [18–74] and median lecocyte count, 17250/μL [1000–318000]. 90% were “de novo” AML and 92% were in first complete remission (1°CR). Cytogenetic risk was as follows: 64% intermediate, 29% high and 7% low. Conditioning regimens were oral BuCy (62%), CyTBI (24%) and intravenous BuCy (12%). Stem cell source was bone marrow (BM) in 46 patients (48%), but the use of peripheral blood (PB) was generalized since 1997. Colony-stimulating factors were used in 52% of total patients. Median time from last treatment was 94 days [30–285]. Results: The median follow-up of this study was 125 months [0–216]. OS at 1, 3 and 5 years were 59%, 46% and 44%. RFS at 1, 3 and 5 years were 60%, 49% and 48%. There was no relapse after 5 years from ASCT. Early mortality (before day +100) was 12% (9 in 11 patients between 1988 and 1999) and late mortality was 47% (34 in 45 patients because of relapse, with no significant difference between 1988–1999 and 2000–2010). Secondary malignancies incidence was 13% (5 in 6 patients suffered from haematologic neoplasms: 4 MDS at 43, 89, 90 and 97 months and 1 Follicular Lymphoma at 50 months), median age of these patients was slightly higher (53, 5 years old) and none of them had received TBI. Multivariable analysis showed that RFS at 5 years was influenced by: disease status at ASCT (55% if 1°CR vs 0% if ≥2°CR/PR/refractory disease, p<0, 0001), leucocyte count at diagnosis (p<0, 0001, without a significant cut-off), ethiologic classification (53% if “de novo” AML vs 19% if secondary AML, p=0, 002), age of recipient (60% if younger than 40 years old vs 45% if older, p=0, 031) and year of ASCT (62% if 2000–2010 vs 44% if 1988–1999, p=0, 043). Other parameters as stem cell source, conditioning regimen or cytogenetic risk had no significance in univariable analysis. Relapse was influenced by the presence of minimal residual disease (MRD) at time of ASCT (p=0, 03, with available data in 47 patients, only since 1997) and by a CD34 cells count higher than 3 × 106/kg (p=0, 04, with available data in 49 patients, only in case of PB as stem cell source). Conclusions: ASCT is an effective procedure of cure in AML patients (global RFS of 48% at 5 years), even in high cytogenetic risk (38% with no significant difference), offering its best outcomes in young patients diagnosed of “de novo” AML without hyperleucocytosis, who have undergone the transplantation in 1°CR since 2000. Disclosures: No relevant conflicts of interest to declare.

Novel Conditioning Regimen for Haploidentical Hematopoietic Cell Transplant for Severe Aplastic Anemia in Children

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5651-5651 ◽  
Author(s):  
Hasan Hashem ◽  
Rawad Rihani ◽  
Eman Khattab ◽  
Mayada Abu Shanap ◽  
Abdelghani Tbakhi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Stem Cell Source ◽  
Cell Source

New hematopoietic cell transplant (HCT) approaches are urgently needed for patients with severe aplastic anemia (SAA) who lack an HLA-identical donor. Haploidentical HCT with post transplant cyclophosphamide (PTCy) represent a potential universal available option for almost all children with SAA. We present a novel conditioning regimen for haploidentical HCT in children with SAA in a center where horse ATG is not available. Conditioning regimen consists of rabbit ATG 2.5 mg/kg/day from day -9 to -7, Fludarabine 30 mg/kg/day from day -6 to -2, Cyclophosphamide 14.5 mg/kg/day from day -6 to -5, Thiotepa 5 mg/kg/day from day -4 to -3, and 4 Gy TBI on day -1 in in two fractions. GvHD prophylaxis consist of PTCy 50 mg/kg/day on days +3 and +4 along with Cyclosporine A and Mycophenolate mofetil (MMF) starting on day +5. Four consecutive children with SAA referred to our center for haploidentical HCT starting in 2018. Median age at HCT was 9 years (5-16) with 3 males and 1 female. All patients were heavily transfused with both blood and platelets prior to referral for HCT. Two patients had strong and one had weak positive anti-HLA antibodies (DSAs) and received desensitization with IVIG, Rituximab and plasmapheresis. One patient received buffy coat infusion on day -1 due to persistent strong DSAs despite desensitization. Median CD34+ dose received was 12 x 10e6, and median CD3+ dose was 29 x 10e6. Donors were all same blood group to patients. All patients successfully engrafted neutrophils at median of 13 days (12-14). Platelets engraftment in 3/4 patients at median of 7 days (5-10). All patients received peripheral blood as stem cell source. Three of four patients survived and doing well at last follow up. One patient had toxic death on day +38 due to chemotherapy related toxicity causing multi-organ failure. Chimerism analysis was full donor in all four patients at median follow up time of 11 months (2-12). Patients were sent home at median of 24 days post HCT. None developed grade 2-4 acute GvHD nor chronic GvHD. Acute GvHD of skin grade 1 stage 1 developed in 2 patient and managed with topical steroids. Viral reactivations consisted of CMV viremia and BK hemorrhagic cystitis in all patients, and have all resolved. No post transplant autoimmune complications. Haploidentical HCT with PTCy represents a quick and first line approach in heavily transfused children with SAA. Although yet limited number of patients, this regimen is feasible and appears to be safe. A great advantage of this regimen is the rapid engraftment of both neutrophils and platelets. Moreover, although using peripheral blood as a stem cell source, there was no severe acute or chronic GvHD. Disclosures No relevant conflicts of interest to declare.

No Significant Benefit of Marrow and Blood HLA-Haploidentical Stem Cell Transplantations Given by Mothers with Long-Term Fetomaternal Microchimerism.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5452-5452
Author(s):  
Ying Wang ◽  
De Pei Wu ◽  
Aining Sun ◽  
Zhengming Jin ◽  
Huiying Qiu
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Chronic Gvhd ◽  
Rank Test ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Standard Intensity ◽  
Significant Difference ◽  
Cell Source

Abstract Non-T-cell-depleted maternal HLA-haploidentical hematopoietic stem cell transplantations(SCT) have been reported feasible based on the hypothesis that long-term fetomaternal microchimerism(FMC) is linked with hyporesponsiveness to inherited paternal antigens(IPAS),but the hypothesis is still in debate due to lack of direct evidence. To determine whether the existence of such microchimerism affect the outcome of maternal HLA-haploidentical SCT, we investigated the outcomes of 18 patients (median age 19) with hematologic malignancies (ALL 8, AML 6, CML 3, NHL 1) who underwent haploidentical SCT from mothers with the same regime from July 2003 to January 2005. Donor was treated with granulocyte colony stimulating factor subcutaneously at a dose of 300μg per day for 5 days before bone marrow harvesting. Leukaphereses were performed using a continuous-flow blood cell separator if CD34+ cells in the bone marrow harvest were less than 4.0×106 cells/kg. Patients with CML or AML in CR received 7.5Gy TBI based standard-intensity regimen combined with cyclophosphamide plus cytarabine. The remaining received non-TBI standard-intensity regimen consisting of cytarabine, busulfan and cyclophosphamide. Antithymocyte globulin(ATG) at a dosage of 2.5mg/kg/day on days −5 to −3 was given as an additional immunosuppressive measure in all patients. To prevent GVHD, patients also received cyclosporin at a dose of 3mg/kg/day as a continuous infusion from day −10, 30mg/kg/day mycophenolate mofetil starting on day −10, and short-term methotrexate administered on days 1, 3, 6, 11 at doses of 15, 10, 10, and 10mg/m2. Among all these patients, microchimerism were confirmed with nested polymerase chain reaction using sequence-specific primers(PCR-SSP) typing for HLA in 10 donor-recipient pairs. In the 2 categories as to whether the microchimeric status of the donor is positive or negative, they had similar characteristics in the background factors such as recipient sex, type of conditioning regime, stem cell source, and disparity of HLA except recipients of positive group had more CML. Engraftment was obtained in all patients. As of august 1, 2005, 5 patients died (1 of relapse, 4 of complication), other 13 patients were alive and free of disease. The 2-year overall survival for the whole cohort was 58%. Although there was a survival advantage for pairs with microchimerism over pairs without it, the influence on outcome was not statistically significant (P=0.9, log-rank test). The cumulative incidences of grade Ò/Ô acute graft-versus-host disease (GVHD) were 39% (95%CI, 17%–64%). Also no significant difference was observed between the two groups. Extensive chronic GVHD developed in 5 of 13 patients who could be evaluated. These results indicate maternal HLA-haploidentical hematopoietic SCT is a acceptable option for patients who lack immediate access to a conventional stem cell source, but the presence of fetomaternal microchimerism may not correlate to the existence of immunological tolerance between mother and offspring.

A Comparison of Stem Cell Source in Recipients of T-Cell Depleted Myeloablative Transplants for Leukaemia: No Difference in Mortality Using BM or PBSC.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 46-46
Author(s):  
B.E. Shaw ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
J. Apperley ◽  
G. Cook ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Increased Risk ◽  
Significant Difference ◽  
Cell Source ◽  
The Impact

Abstract The use of GSCF-mobilised Peripheral Blood Stem Cells (PBSC) for unrelated donor (UD) transplantation has increased dramatically since 2000. The association of PBSC with more rapid engraftment and with an increase in chronic Graft versus Host Disease (GvHD), compared to bone marrow (BM) has been reported in a number of studies. More recently the use of PBSC has been associated with an increase in transplant related mortality (TRM) and decrease in survival (OS) in T-cell replete transplants. We sought to analyse the impact of PBSC compared to BM in a cohort of UD transplant recipients, where T-cell depleting agents (in-vivo campath in >90%) were included in the transplant conditioning. The study included 145 patients transplanted between January 2000 and March 2006: CML- 35 in 1CP; acute leukaemia (AML in 61, ALL in 49)-110 in CR1 or 2. All had myeloablative conditioning regimens and received grafts with 9–10/10 matched HLA alleles. 86 patients received BM and 59 PBSC. There were no associations between the stem cell source and any transplant variable (including disease and stage). There was a trend to an increased use of PBSC in patients with a single antigen mismatch (p=0.052). All evaluable patients achieved neutrophil engraftment, with a significantly faster time to engraft in recipients of PBSC compared to BM (16 vs 20 days; p=0.0003). The incidence of acute GvHD was 46% (grade I in 50%, II in 41%, III in 8%, IV in 2%). This was significantly higher in recipients of PBSC (60%) compared to BM (36%; p=0.006), however there was no increase in either II/IV (p=0.69) or III/IV (p=0.18) disease in PBSC recipients. In univariate analysis, the presence of a single HLA mismatch (p=0.026) was the only other variable to be associated with an increase in acute GvHD. In a logistic regression model including both these variables, the use of PBSC remained significantly associated with an increase in aGvHD (OR=2.3; 95% CI 1.1,4.7;p=0.020). The TRM was 14%, 27% and 39% at 100 days, 1 and 5 years respectively. At none of these time points was the stem cell source associated with a significant difference in TRM. The 5-year incidence of chronic GvHD was 58% (BM 55%, PBSC 60%; NS), extensive disease in one third, and of relapse was 61% (BM 60%, PBSC 62%; NS). The 5-years OS was 41% with a median follow-up of 3.4 years (0.5–7.1). This was 44% using PBSC and 40% using BM (NS). In conclusion, although we observed an increase in acute GVHD with PBSC this was only of grade 1 disease. We found no association between the use of PBSC and an increased risk of chronic GVHD or of a worse transplant outcome, when compared to BM, in recipients of T-cell depleted myeloablative transplants for leukaemia.

Comparison of PBSC Vs Cord Blood (CB) As Stem Cells Source for Reduced-Intensity Conditioning Regimen (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Adult Patients with Haematological Diseases: A Single Centre Analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3108-3108
Author(s):  
Amandine Lebourgeois ◽  
Marion Loirat ◽  
Benoit Tessoulin ◽  
Elsa Lestang ◽  
Pierre Peterlin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Single Centre ◽  
Stem Cell Source

Abstract Abstract 3108 Introduction: RIC regimens are increasingly used for allo-SCT in older patients or patients with co-morbidities. The FB2 regimen (Fludarabine 120–150 mg/m2 + I.V. Busulfan 6.4 mg/Kg + ATG 5 mg/Kg) using PBSC as stem cell source is currently the most widely used RIC regimen in many European centres. On the other hand, in patients without a suitable HLA-matched donor, the use of umbilical cord blood stem cells for allo-SCT (uCBT) is increasingly considered, especially using the RIC regimen developed by the Minneapolis group. Series comparing PBSC vs CB as stem cells source for RIC allo-SCT are still scarce and using various RIC regimens before allo-SCT. Patients and Methods: This retrospective single centre analysis compared two homogeneously treated cohorts of patients who had received between January 2007 and November 2010 in our department either a FB2/PBSC allo-SCT (n=52, males: 61%; median age: 59 years (range: 22–70)) or a FC-TBI/uCBT (Fludarabine 200 mg/m2 + Cyclophosphamide 50 mg/Kg + TBI 2 Grays regimen; n=39, males 49%; median age 56 years (range: 22–70). Except for age (p=0.03), there were no significant differences between the 2 groups regarding patients and diseases characteristics: gender (p=0.22), interval between diagnosis and transplant (PBSC: 9 months vs CB: 10 months, p=0.85), disease type (PBSC: myeloid disease 63% vs CB: 67%, p=0.75), status at transplant (complete remission PBSC: 77% vs CB: 67%, p=0.28), prior auto-SCT (PBSC: 35% vs CB: 33%, p=0.90). Donors in the PBSC group were as follows: sibling donors, n=30; HLA-MUD n=20, mismatched unrelated n=2. All patients from the CB group received 2 CB units (HLA matching 4/6 n=25; 5/6 n=53). As for GVHD prophylaxis, patients received cyclosporine (CsA) alone in case of an HLA-identical sibling donor, and CsA+ mycophenolate mofetyl in all other cases. None of the patients from the PBSC group received G-CSF after transplant, while it was administered to all CB recipients. Results: Median follow-up was respectively 19 and 20 months for the PBSC and the CB groups (p=NS). Engraftment and median time for neutrophils recovery were similar between the 2 groups: PBSC: 96% vs CB: 90%, p=0.22; and 17 days (range: 0–39) vs 16 days (range: 8–60), p=0.88, respectively. The median time for platelets recovery (&gt;20000/mm3) was significantly higher in the CB group: 38 days (range: 13–150) vs PBSC: 0 days (range: 0–186) (p&lt;0.0001). The cumulative incidences of grade II-IV and grade III-IV acute GVHD were comparable between both groups: PBSC: 31% and 15% vs CB: 26% and 8% (p=0.72 and p=0.28) as also the 2-years incidence of chronic GVHD: PBSC: 35% vs uCBT: 25%, p=0.54. 2-years NRM was significantly higher after uCBT: 26% vs 6%, p=0.02. Finally, there were no differences between the two groups in terms of 2-years OS, DFS and Relapse Incidence: PBSC: 62.3% vs CB: 60.8% (p=0.51); 58.7% vs 50.4% (p=0.43) and 36% vs 23% (p=0.31). In multivariate analysis, the source of stem cells (CB) remains associated with NRM (HR: 0.16, 95%CI: 0.05–0.5, p=0.001) but was not predictable for survivals. Conclusion: Our study suggests that RIC uCBT is a valid alternative in patients lacking an HLA-matched related or unrelated donor and candidate for RIC allo-SCT. Prospective and randomized studies are warranted in order to establish the definitive role of uCBT, especially in patients with acute leukemia, where CB cells may offer a rapidly available source of stem cells in diseases with high tumor kinetics. Disclosures: No relevant conflicts of interest to declare.

A Comparison of Stem Cell Source in Adult and Paediatric Recipients of T-Cell Depleted Myeloablative Transplants for Standard Risk Leukaemia: No Difference in Mortality Using BM or PBSC.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1205-1205
Author(s):  
Bronwen E Shaw ◽  
Jane Apperley ◽  
Nigel H. Russell ◽  
Charles F. Craddock ◽  
Effie Liakopoulou ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source ◽  
Standard Risk

Abstract Abstract 1205 Poster Board I-227 The use of GSCF-mobilised Peripheral Blood Stem Cells (PBSC) for unrelated donor (UD) transplantation has increased dramatically since 2000. The association of PBSC with more rapid engraftment and with an increase in chronic Graft versus Host Disease (GvHD), compared to bone marrow (BM) has been reported in a number of studies. More recently the use of PBSC has been associated with an increase in non relapse mortality (NRM) and decrease in survival (OS) in T-cell replete transplants. We have previously reported outcome data in 145 patients who received an unrelated donor transplant for leukaemia. In that study we reported an increase in mild acute GvHD using PBSC, but no other significant differences in outcome. We have now doubled the cohort and report our findings on 320 patients here. In this group all of the patients received pre-transplant serotherapy (Alemtuzumab = 306, ATG = 14) as part of myeloablative conditioning prior to an HLA-matched UD allograft. Patients were transplanted between January 2000 and August 2007: CML in 1CP (n=102) and acute leukaemia in CR1/2 (AML in 105, ALL in 144). 190 patients received BM and 130 PBSC. The median age of the recipients was 28.9 years (10months - 58years). There was no significant difference in age between those receiving BM or PBSC.98% and 96% of patients receiving PBSC and BM achieved neutrophil engraftment (NS), with a significantly faster time to engraftment in recipients of PBSC compared to BM (14 vs 20 days; p<0.001). The incidence of acute GvHD was significantly higher in recipients of PBSC (64%) compared to BM (51%; p=0.022), however there was no increase in grade III/IV (p=0.420) disease in PBSC recipients. The incidence of chronic GvHD at 6 years was 61% in the BM recipients and 55% in the PBSC recipients (NS), with no difference in the incidence of extensive disease. The 5-years OS was 55% in BM recipients, with a median follow-up of 59 months, compared to 54% in PBSC recipients at a median follow-up of 38 months (NS). The incidence of neither disease relapse nor NRM was significantly different between groups (relapse at 5 years: BM 44%, PBSC 36%; p=0.112, and NRM at 5 years: BM 22%, PBSC 24%; p=0.751). In view of the fact that there were more CML patients in the BM group and more AML patients who received PBSC (the distribution of ALL patients was similar) (p=0.051), we performed a subgroup analysis. The pattern of results for each outcome, dependant on the use of BM or PBSC, in patients with CML and those with acute leukaemia were similar to those reported in the group overall. In conclusion, we have confirmed the results of our previous smaller study, showing the only significant difference in clinical outcome between PBSC and BM to be a higher incidence in the occurrence (but not grade) of acute GvHD. We found no association between the use of PBSC and an increased risk of chronic GVHD or of a worse transplant outcome, when compared to BM. We suggest that either stem cell source can be used with a similar outcome in adult and paediatric recipients of T-cell depleted allografts for standard risk leukaemia. Disclosures: Apperley: Novartis: Consultancy, Honoraria.

scholarly journals Influence of Donor Type, Stem Cell Source and Conditioning Regimen on Transplant Outcomes after Haploidentical Transplant with Post Transplant Cyclophosphamide for Lymphoma: A Report of the EBMT Lymphoma Working Party

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 484-484
Author(s):  
Ali Bazarbachi ◽  
Ariane Boumendil ◽  
Hervé Finel ◽  
Luca Castagna ◽  
Alida Dominietto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lymphoma ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Abo Incompatibility ◽  
Stem Cell Source ◽  
Cell Source ◽  
Grade Ii ◽  
Grade Iii

Abstract Allogeneic stem cell transplantation (SCT) is potentially curative for patients with lymphoma who progress after autologous SCT. For patients with no HLA identical donor, haploidentical transplant is becoming the major source of alternative donors, particularly with the use of post transplant cyclophosphamide (ptCy). However, there are little data on whether outcomes are affected by the characteristics of the haploidentical donor, the stem cell source or the conditioning. To address this important subject, we identified 474 adult patients (35% females; median age 41 years; range 18-72) with Hodgkin lymphoma (HL-240; 51%), peripheral T cell lymphoma (PTCL-88; 19%), diffuse large B cell lymphoma (DLBCL-77; 16%), mantle cell lymphoma (MCL-40; 8%) or follicular lymphoma (FL-29; 6%), who received a haploidentical SCT (haploSCT) with ptCy between 2010 and 2016 at EBMT participating centers. Patients, donors and transplant characteristics are summarized in Table 1. Median follow-up of alive patients was 32 months (range 3-93). Engraftment by day 100 was successful in 95% of patients. In multivariate Cox analysis (MVA), the use of peripheral blood stem cells (PBSC) positively affected engraftment (HR=1.53; p<0.001). Day 100 acute GVHD (aGVHD) grade II-IV and grade III-IV were diagnosed in 32% and 8% of patients, respectively, and were significantly affected in multivariate analysis by PBSC (HR=2.1 p<0.001 for grade II-IV and HR=4.5 p=0.001 for grade III-IV). The use of sibling haploidentical donors increased the risk of aGVHD grade II-IV (HR=1.87 p=0.01) whereas a CMV negative donor in a positive recipient increased the risk of aGVHD grade III-IV (HR=5.3 p=0.04). The 2-year cumulative incidence of chronic GVHD (cGVHD) and extensive cGVHD were 25% and 9%, respectively. On MVA, male patients had a higher risk of cGVHD and extensive cGVHD (HR =1.7 p=0.03; and 2.8 p=0.04, respectively), whereas a male donor was protective (HR= 0.6 p=0.02; and 0.3 p=0.008, respectively). The risk of cGVHD and extensive cGVHD was also higher for patients in PR (HR 1.7 p=0.03; and 2.4 p=0.04, respectively). The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 29% and 19%, respectively. In MVA, both CIR and NRM were negatively affected by the lymphoma subtype and by disease status at transplant, both being highest for DLBCL and for advanced disease. Older patient age was associated with a higher NRM but with a lower CIR. The type of conditioning regimen and CMV compatibility also influenced NRM, whereas ABO incompatibility influenced CIR. The 2-year progression free survival (PFS) and overall survival (OS) for HL were 57% and 72% respectively; 54% and 62% for PTCL; 35% and 35% for DLBCL; 52% and 61% for MCL and 56% and 56% for FL. In MVA, CR at SCT significantly improved PFS and OS whereas a diagnosis of DLBCL as well as a CMV donor positive/recipient positive transplant negatively affected PFS and OS. In conclusion, this is the largest study on the influence of donor characteristics, stem cell source and conditioning in haploSCT with ptCy for lymphoma. These results provide critical information to help selecting the best donor in the setting of haploSCT for lymphoma. Our results indicate that the use of PBSC significantly improves engraftment but increases the risk of acute GVHD. Conditioning only influenced NRM but had no effect on PFS or OS. The use of female donors increases the risk of chronic GVHD. Of note, PFS and OS are mostly influenced by disease characteristics (i.e disease status and lymphoma subtype), whereas, with the exception of CMV compatibility, no other donor characteristics (donor age and gender, relationship of the donor to the recipient, degree of HLA mismatch or ABO incompatibility, prior donor pregnancy) impact on PFS or OS, supporting the use of any haplo-identical family member as a donor. Table. Table. Disclosures Tischer: Jazz Pharmaceuticals: Other: Jazz Advisory Board. Mohty:MaaT Pharma: Consultancy, Honoraria. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs. Sureda:BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria; Merck: Consultancy, Honoraria; Roche: Honoraria.

scholarly journals Post-Transplant Cyclophosphamide Versus Antithymocyte Globulin in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation from HLA-Identical Sibling Donors: A Retrospective Analysis from the Acute Leukemia Working Party of the EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 148-148
Author(s):  
Giorgia Battipaglia ◽  
Myriam Labopin ◽  
Rose-Marie Hamladji ◽  
Didier Blaise ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cyclosporine A ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
The Other ◽  
Free Survival ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source

Introduction. In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-identical matched sibling donor (MSD), use of cyclosporine A in association with methotrexate has been the main graft-versus-host disease (GVHD) prophylaxis strategy. Addition of antithymocyte globulin (ATG), especially when using peripheral blood stem cells (PBSC) as source, has also been shown to favor lower rates of chronic GVHD. More recently, use of post-transplant cyclophosphamide (PTCY) in the haploidentical setting resulted in low incidences of both acute and chronic GVHD. Its use has therefore been subsequently reported in other donor settings, including MSD. The aim of our study was to compare GVHD prophylaxis containing either PTCY or ATG in patients diagnosed with acute myeloid leukemia and undergoing allo-HSCT from a MSD. Methods. This was a retrospective study from the EBMT registry. Included were adult patients undergoing their first allo-HSCT during the period 2008-2018 and who were in complete remission at time of allo-HSCT. Results. Globally, 197 and 1,913 patients receiving either PTCY or ATG, respectively, were identified who fulfilled inclusion criteria. Patients in the PTCY group were younger (median age 47 versus 54 years, p&lt;0.01) and had undergone allo-HSCT more recently (median year of allo-HSCT: 2015 versus 2014, p&lt;0.01). Peripheral blood was the more frequently used stem cell source, this being significantly more frequent in the ATG group (95% versus 70%) than in the PTCY group (p&lt;0.01). The conditioning regimen was more frequently myeloablative in the PTCY group (59% versus 48% in the ATG group, p&lt;0.01). Cyclosporine-A alone was the most used systemic immunosuppressive agent associated with either PTCY (22%) or ATG (28%), while 34% and 29% of patients in the ATG group and 7% and 12% in the PTCY group also received either methotrexate or mycophenolate mofetil along with cyclosporine A. No statistical differences were observed for incidence of grade II-IV acute GVHD at 100 days after allo-HSCT, this being 19% versus 17% in the PTCY and ATG groups, respectively (p=0.81). On the other hand, a significantly higher incidence of chronic GVHD at 2 years was observed with the use of PTCY (37% versus 30%, p&lt;0.02) and for extensive chronic GVHD (16% versus 12%, p&lt;0.01) as compared to ATG. There was no impact of conditioning intensity on GVHD incidence. No statistical differences were observed on univariate analysis for all other transplant outcomes, with a leukemia-free survival (LFS) of 55% versus 58%(p=0.75), overall survival (OS) of 64% versus 65% (p=0.61), GVHD-free, relapse-free survival (GRFS) of 44% versus 49% (p=0.19), relapse incidence (RI) of 36% versus 32% (p=0.56) and non-relapse mortality (NRM) of 8% versus 10% (p=0.78). Of note, the cumulative incidences of death due to GVHD were 4.4% and 4% in the PTCY and ATG groups, respectively (p=0.53). Also, there were no differences between the 2 groups for death due to infections: 6% in the PTCY group and 6.3% in the ATG group, respectively (p=0.49). On multivariate analysis, these results were confirmed, with a higher risk of chronic GVHD of any grade (HR=1.41, 95%CI 1.03-1.92; p&lt;0.01) and extensive chronic GVHD (HR=1.68, 95%CI, 1.07-2.62; p&lt;0.01) with PTCY, and no differences with respect to the other outcomes. We also observed that, regardless of the use of PTCY or ATG, use of PBSC was associated with lower RI (HR=0.64, 95% CI 0.46-0.89; p&lt;0.01), higher LFS (HR=0.71, 95% CI 0.53-0.95; p&lt;0.03), and OS (HR=0.72, 95% CI 0.52-0.99; p&lt;0.05). On the other hand, we found no statistical differences in terms of both acute GVHD (HR=0.73, 95%CI, 0.48-1.12; p=0.15) and chronic GVHD (HR=0.83, 95% CI 0.56-1.21; p=0.33) according to stem cell source. These results were also confirmed in a matched-pair analysis. Conclusion. In conclusion, our results highlight that in the HLA-identical sibling setting, the use of ATG provides similar outcomes to those seen with PTCY except for chronic GVHD for which a protective effect of ATG is confirmed as previously reported by different other studies. Disclosures Blaise: Sanofi: Honoraria; Molmed: Consultancy, Honoraria; Pierre Fabre medicaments: Honoraria; Jazz Pharmaceuticals: Honoraria. Chevallier:Incyte: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Daiichi Sankyo: Honoraria. Socie:Alexion: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

scholarly journals Allogeneic and Autologous Hematopoietic Transplants Can be Safely Performed after COVID-19 Infections

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2855-2855
Author(s):  
Jeremy L. Ramdial ◽  
Rima M. Saliba ◽  
Amin M. Alousi ◽  
Gabriela Rondon ◽  
Julianne Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Stem Cell Source ◽  
Underlying Malignancy ◽  
Hematopoietic Transplantation ◽  
Cell Source ◽  
History Of

Abstract We are in the midst of a pandemic with the COVID-19 virus, a pathogen with potential severe manifestations. A major clinical question is whether it is safe to undergo hematopoietic stem cell transplantation (HSCT) shortly after COVID-19 infection. A total of 21 patients received HSCT following a diagnosis of COVID-19 infection at our institution between 7/30/2020 and 4/14/2021. The majority (n=13, 62%) received an allogeneic (ALLO) HSCT from an HLA-matched related (n=5), -matched unrelated (n=6), or haploidentical (n=2) donor. The remaining 8 patients received autologous (AUTO) HSCT. Among ALLO-HSCT recipients, 4 (31%), 5 (38%), 3 (23%), and 1 (8%) patients had grade 1, 2, 3, and 4, manifestations respectively, scored according to the WHO COVID-19 infection severity grading system. Among AUTO-HSCT recipients, 5 (62%), 1 (12%), and 2 (25%) patients had grade 0, 1, and 2 manifestations, respectively. All patients had resolution of COVID-19 symptoms before HSCT. In recipients of ALLO-SCT, the median time from diagnosis of the COVID infection to HSCT was 134 (range: 55-311) days. Median age of recipients was 53 (range: 17-71) years and the majority (69%) of patients were male. Only one patient was &lt;18 years old, and 38% were &gt;60 years. Patients received ALLO-HSCT for treatment of acute myeloid leukemia or myelodysplastic syndrome (n=7, 54%), acute lymphoblastic leukemia (n=2, 15%), chronic lymphoblastic leukemia (n=2, 15%), and Hodgkin's (n=1, 8%) or non-Hodgkin's lymphoma (n=1, 15%). Most (62%) patients were not in remission at the time of HSCT. The median hematopoietic cell transplant-co-morbidity index (HCT-CI) score was 3 (range 0-6); one patient had a history of diabetes and another of hypertension before HSCT. Conditioning regimen was myeloablative in 61%, and stem cell source was peripheral blood (PB) in 92% of transplants. Median time to neutrophils engraftment was 15 (range: 10-20) days. With a median follow-up of 3.5 (range: 0.4-8) months since ALLO-HSCT, two patients died and another two experienced progression of the underlying malignancy. Three patients were diagnosed with grade 2 and none with grade 3 or 4 acute graft-versus-host disease (GvHD). The deaths occurred among patients with COVID-19 infection grade 2 and 3. The primary cause of death was attributed to alveolar hemorrhage/pneumonitis (no organism identified) and acute GvHD, respectively. Overall survival was 89% (95% confidence interval [CI]:43-98) and 76% (95% CI 33-93) at 3 and 6 months, respectively. In recipients of AUTO-HSCT, the median time from diagnosis of the COVID-19 infection to HSCT was 55 (range: 20-157) days. Median age of recipients was 55 (range: 34-75) years, and the majority (62%) of patients were male. One (12%) patient was &gt;60 years. Patients received AUTO-HSCT for treatment of Hodgkin's (n=1, 15%) or non-Hodgkin's (n=4, 50%) lymphoma, or multiple myeloma (n=3, 37%). Six (75%) patients were in remission at the time of HSCT. The median HCT-CI score was 2 (range 0-6). None of the patients had a history of diabetes or hypertension before transplant. Conditioning regimen was myeloablative and stem cell source was PB for all patients. Median time to neutrophils engraftment was 10 (range: 9-13) days. With a median follow-up of 4 (range: 0.8-9) months since AUTO-HSCT, one patient with grade 1 COVID infection died as a result of a candida/cytomegalovirus infection, and none of the patients experienced progression of the underlying malignancy. Overall survival was 100% and 75% (95% CI 13-96) at 3 and 6 months respectively. After HSCT, one ALLO and two AUTO asymptomatic patients had a positive nasal swab COVID-19 PCR assay possibly due to delayed shedding of the virus. None of the 21 patients developed active COVID infections post-transplant. In conclusion, allogeneic and autologous hematopoietic transplantation can be performed in patients after COVID-19 infection. Two of 13 allogeneic and one of 8 autologous recipients experienced non-relapse mortality, none directly related to COVID-19 infection. Patients recovering from COVID-19 infection should be considered eligible for hematopoietic transplantation as clinically indicated. Disclosures Shpall: Magenta: Honoraria; Affimed: Patents & Royalties; Novartis: Honoraria; Navan: Consultancy; Magenta: Consultancy; Axio: Consultancy; Adaptimmune: Consultancy; Bayer HealthCare Pharmaceuticals: Honoraria; Novartis: Consultancy; Takeda: Patents & Royalties. Chemaly: Other: Other: Compensation: I am a consultant and advisor on companies who are developing new agents such as Merck, Ansun, and Janssen.

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