The ANALYSIS of Chimerism IN ACTIVATED T Lymphocites CD25+ Improves the CAPACITY of the T Lymphocytes CD3+ Chimerism Dinamic to Predict COMPLICATIONS AFTER Allogenic STEM CELL TRANSPLANTATION.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4307-4307
Author(s):  
Noriega Concepcion Victor ◽  
Gayoso Jorge ◽  
David Serrano ◽  
Rodriguez Macias Gabriela ◽  
Pascual Balsalobre ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Lymphocytes ◽  
Stem Cell Transplantation ◽  
Whole Blood ◽  
Allogenic Stem Cell Transplantation ◽  
Activated Lymphocytes ◽  
Cell Lineages ◽  
Chimerism Analysis ◽  
Prediction Of Complications

Abstract Abstract 4307 Introduction Complications after Allogenic Stem Cell Transplantation (Allo-SCT) are influenced by the immunological fenomena associated to the alloreactivity/allotolerance between donor and recepient. In this context, the usefulness of chimerism quantification in T lymphocytes for the prediction of complications after Allo-SCT is well known. However, to our knowledge, there is no information on the utility of chimerism analysis in activated lymphocytes (CD25+). Objective To stablish an asociation betwen the more common complications post Allo-Tph (aGVHD, cGVHD, relapse, reject), and the chimerism dynamics in CD25+ activated lymphocytes in the early period post-transplantation, trying to predict the patients with more risk of suffering from this complications. Materials and Methods The study included 38 Allo-SCT (17 NMA, 21 MA; 7 Haploidentical, 13 non-related donor, 18 identical donor; 7 UCB, 5 BM, 26 PB). Chimerism analysis was performed every 2 weeks until complete chimerism (CC) was achieved, and every 3 months thereafter. Follow up was censored when patients received DLI or 2nd Allo-SCT.Chimerism quantification was performed by microsatellite PCR (STR-PCR; AmpFlSTR SGM Plus; Applied Biosystems) on DNA obtained from peripheral blood and purified cell lineages (95% putity) by immunomagnetic technology (Miltenyi Biotec). Results Table 1 shows the results at day +30 for T and activated lymphocytes (CD3+ and CD25+) allocating patients in two groups depending on the relative percentage of recipient cells (% rec) in both cell lineages. 20 patients were in CC in CD25+, maintening this CC during the study. 18 patients were found in MC in CD25+ (18/38 MC). 1/18 was in CC in CD3+ TL, and 10/18 were in CC in whole blood. 17/18 were in MC both in CD3+ and CD25+ lymphocytes, Although no statistical significance is achieved due to the reduced sample size, patients in the first group (% rec higher in activated that in T lymphocytes) tend to achieve CC later and to show higher risk of developing complications such as acute and chronic GVHD, relapse or rejection. Conclusions A higher incidence of complications post Allo-SCT (aGVHD, cGVHD, relapse, rejection) in patients with % of recipient in CD25+> % recipient in CD3 at day 30. Chimerism analysis in activated lymphocytes (CD25+) is of great utility after Allo-SCT since it allows beter prediction of complications than standard follow up of whole blood or T lymphocytes. Disclosures: No relevant conflicts of interest to declare.

Low Relapse without Excessive Transplant-Related Mortality Following Allogeneic Stem Cell Transplantation in Patients with High Risk Secondary Acute Myeloblastic Leukaemia and Myelodysplastic Syndromes, Long-Term Outcomes in a Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4308-4308
Author(s):  
Jean El-cheikh ◽  
Luca Castagna ◽  
Sabine Furst ◽  
Catherine Faucher ◽  
Benjamin Esterni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Allogenic Stem Cell Transplantation ◽  
Related Mortality

Abstract Abstract 4308 Allogenic stem cell transplantation (Allo-SCT) as a therapy for secondary acute myeloid leukaemia (sAML) and myelodisplastic syndromes (MDS) is the most powerful treatment option. However, (Allo-SCT) is also complicated by a high risk for treatment-related morbidity and mortality. We analysed retrospectively the data of 70 patients transplanted at our institution from June 1995 to december 2008, 44 patients (63%) with sAML and 26 patients (37%) with MDS was treated with (Allo-SCT); median age at diagnosis was 41 years, (15-70), and the median age of 42, 5 years (16-70) at transplantation; The conditioning regimen was myeloablative combining (cyclophosphamide and TBI) in 16 patients (23%) and 54 patients (77%) was with a reduced intensity conditioning (RIC) regimens combining fludarabine, busulfan, and antithymocyte globulin; 11 patients (16%) were infused with bone marrow (BM), 55 patients (79%) peripherical blood stem cells (PBSC), and 4 patients (5%) cord blood cells; in 49 cases (70%) donor was a HLA identical sibling and in 21 (30%) was a matched unrelated donor; 41 patients (59%) carried high risk cytogenetic features, like (7q-, 5q-, > 3 alterations), while was normal in 24 patients (34%), and in 5 patients (7%) was unknown. Disease status at transplantation was as follow: CR in 24 patients (34%), 34 patients (49%) was refractory or in progression after treatment, and 12 patients (17%) was with a stable disease. With a median follow-up of 55 months (3-150), 30 patients (43%) are alive, the overall survival OS at 2 years and 5 years was 48 % and 39% respectively, and after ten years of follow up, OS was 30%, 95%CI [17.8-50.8]. We observed also that 26 % of refractory patients and 54% of patients in CR are alive at five years of transplantation. The probability of progression after transplantation at five and ten years was 31% with 95%CI [20.-46.5]. 2 years and 5 years treatment related mortality (TRM) was 23% and 26% respectively, and no modification at ten year, 95%CI [14.3-37.3]. TRM occurred in 16 patients (23%). Cause of death was; infections in 5 patients (7%), GvHD in 3 patients (4%), GvHD and infection in 3 patients (4%), multi organ failure (MOF) in 5 patients (7%). In multivariate analysis; OS, PFS or TRM, were not influenced by donor type (HLA id sibling vs others), conditioning regimen (RIC vs MAC), and stem cell source (bone marrow vs PBSC). Allogenic stem cell transplantation can be considered as a good option for the treatment of patients with high risk sAML and MDS when compared with the remission rate at five years of the other nonallogeneic SCT therapies. Disclosures: No relevant conflicts of interest to declare.

Dynamics of Chimerism In Regulatory T Lymphocytes (Treg; CD4+/CD25+) After Allogeneic Stem Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1328-1328
Author(s):  
Víctor Noriega ◽  
Carolina Martinez-Laperche ◽  
David Serrano ◽  
Gabriela Rodriguez-Macias ◽  
Mi Kwon ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Lymphocytes ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Small Sample ◽  
Mixed Chimerism ◽  
Group 2

Abstract Abstract 1328 Introduction: CD4+CD25+ regulatory T-cells (Treg) play an important role in inducing and maintaining allogeneic tolerance and can inhibit graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). However, the dynamics of donor and recipient Treg cell populations after Allo-SCT has not been studied yet. Objective: To analyze the dynamics of chimerism in Tregs and compare it to that of T lymphocytes (TL; CD3+) and whole blood leukocytes (WBL). Material and Methods: The study includes 53 patients subjected to Allo-SCT (myeloablative and non-myeloablative). PB samples were obtained weekly during the first month and every 14 days after day +30 until complete chimerism (CC) was achieved, and at fixed time-points (+30, +60, +90, +180, +365) thereafter. TL and Tregs were purified from PB until CC was achieved using inmunomagnetic technology (Miltenyi Biotec; CD3+ Microbeads and CD4+/CD25+ Treg Isolation Kit, respectively). Chimerism analysis was performed by microsatellite PCR (STR-PCR; AmpFlSTR SGM Plus; Applied Biosystems) on genomic DNA obtained from WBL as well as on cell lysates obtained from purified TL and Tregs. Complete chimerism was considered in samples with percentage of recipient cells <1% (sensitivity of the STR-PCR) for WBL samples and <5% (minimum purity of 95% as estimated by flow cytometry) for purified cell lineages. Results: Median follow up for the whole cohort of patients was 338 days. CC was spontaneously achieved in WBL, TL and Tregs in 45/53 patients (85%) in a median time of 35.41, 38.8 and 42.5 days respectively. 5/3 patients (9%) suffered from graft failure/rejection showing mixed chimerism (MC) with increasing percentages of recipient cells both in WBL and leukocyte lineages. 3/53 patients (6%) maintained mixed chimerism (MC) in WBL and leukocyte lineages at day +180, with no signs of graft rejection or disease relapse. Analysis of the chimerism dynamics of those patients who spontaneously achieve CC revealed two different groups: Group 1 included 25/45 patients who achieved CC at the same time in WBL, TL and Tregs. Group 2 included 20/45 patients who achieved CC in WBL while maintaining MC in TL and Tregs. Interestingly enough, 9/20 patients from Group 2 maintained MC in Tregs 7–75 days after achieving CC in both WBL and TL (Figure 1). In a preliminary analysis, the small sample size precluded from obtaining statistically significant associations between the dynamics of chimerism in Tregs and the development of complications such as relapse or GVHD after SCT. Conclusions: To our knowledge, this is the first study dealing with Treg chimerism after SCT. We have shown it is feasible and can be performed on a routine basis together with standard lineage specific chimerism follow up. Although there is an association between chimerism dynamics in Tregs and TL, this is not absolute and a percentage of patients maintain residual Tregs of recipient origin after WTL and TL have become of complete donor origin. In this small cohort, Treg chimerism did not influence the development of post-SCT complications. Analysis of a larger and more homogeneous cohort would allow establishing the usefulness of Treg chimerism testing for the management of transplanted patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals PB2382 FOLLOW UP POST ALLOGENIC STEM CELL TRANSPLANTATION IN MOROCCO: ABOUT 28 PATIENTS

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 1059-1060
Author(s):  
S. Haidouri ◽  
K. zine Filali ◽  
M. ababou ◽  
E. mahtat ◽  
M. mikdame ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogenic Stem Cell Transplantation

Transient and Myeloid Leukemia in Children with Down Syndrome Mosaic

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2539-2539
Author(s):  
Alexandra Kolenova ◽  
Katarina Reinhardt ◽  
Michaela Nathrath ◽  
Claudia Rossig ◽  
Arend von Stackelberg ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Trisomy 21 ◽  
Myeloid Leukemia ◽  
Patient Specific ◽  
Allogenic Stem Cell Transplantation ◽  
Gata1 Mutation

Abstract Abstract 2539 Introduction: Transient leukemia (TL) occurs in 5 to 10% of newborns with Down syndrome (DS). In almost all cases it resolves spontaneously within 3 months, but 20–25% of the children develop myeloid leukemia (ML-DS) until the age of 4 years. TL and ML-DS can occur also in children without any clinical signs of Down syndrome, but with constitutional trisomy 21 due to mosaicism. It can be difficult to diagnose TL or ML-DS in these children and the treatment strategies have not been defined. Patients/Material: Between 1/2002 and 7/2011, 15 newborns and infants were diagnosed with DS mosaic. Nine of them presented with TL and 8 children suffered from ML-DS; 2 of them with a history of TL (table 1). In children without any stigmata the special morphology and immunophenotype of blasts triggered the screening for GATA1 mutation and trisomy 21 mosaic. Diagnostic work-up was performed according to standard guidelines: morphology, immunophenotyping (IP), cytogenetics and FISH (trisomy 21), molecular genetics (GATA 1 mutation screening). Screening of GATA1 mutations was done with direct sequencing of PCR product (Exon1, Exon2, and Exon3). For monitoring of GATA1 mutant clone qPCR have been used with patient specific TaqMan probes and primers. Mosaic was detected by cytogenetics or FISH in bone marrow, blood and/or fibroblasts. Results: All newborns with TL achieved complete remission (CR). Due to clinical symptoms caused by the leukemic blasts, in 3 children low-dose cytarabine was applied. One patient died due to cardiovascular failure. In all patients GATA 1 mutation was confirmed. Minimal residual disease by qPCR (mutation-specific probes) or immunophenotyping (IP) revealed negativity in 3 out of 3 children monitored (follow-up 2 to 10.1 yrs). Two children with (unknown) trisomy 21 mosaic were diagnosed as acute megakaryoblastic leukemia (AMKL) and treated according the high risk arm of the AML-BFM 2004 including allogeneic stem cell transplantation (one child), GATA1 mutation was identified retrospectively. Both children are alive in CR. Six children with ML-DS were initially treated according the AML-BFM protocol. After ML-DS was confirmed, therapy was continued with the intensity reduced schedule according to the ML-DS 2006 protocol. All children are still in CR (follow-up 1.5 to 6.7 years, median 2.4 yrs). This was confirmed by MRD-monitoring, which achieved negativity after two treatment elements (qPCR <10−4 n=3; IP <10−3 n=6). In one child a distinct refractory myeloid leukemia population (GATA1mut negative/trisomy 21 negative) arose after the 1st induction. Due to treatment refractory, allogenic stem cell transplantation was applied. Conclusions: GATA1 mutated leukemia has to be excluded in all young children with AMKL (<5years old) to prevent overtreatment. Treatment with reduced intensity protocol like ML-DS 2006 seems to be effective and sufficient in children with trisomy 21 mosaic and GATA1 mutated ML-DS. Disclosures: No relevant conflicts of interest to declare.

Ponatinib Is Well Tolerated and Active In Patients With Relapsed/Refractory Philadelphia Positive Acute Lymphoblastic Leukemia (PH+ ALL) and Advanced Phase Of Chronic Myelogenous Leukemia (CML) Harbouring T315I Mutation: The Bologna Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3911-3911
Author(s):  
Cristina Papayannidis ◽  
Caterina De Benedittis ◽  
Simona Soverini ◽  
Ilaria Iacobucci ◽  
Maria Chiara Abbenante ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Molecular Mechanisms ◽  
Myelogenous Leukemia ◽  
Serum Lipase ◽  
Allogenic Stem Cell Transplantation ◽  
T315i Mutation ◽  
Grade Iii

Abstract Background Ponatinib, a potent third generation pan BCR-ABL inhibitor, has recently shown relevant activity against native and mutant forms of BCR-ABL, including the TKI resistant T315I mutant. The aim of this compassionate protocol was to confirm and evaluate the efficacy and the safety of the compound in patients with advanced Ph+ ALL and CML. Design and Methods Ponatinib was obtained through a compassionate use named patient program, approved by ARIAD Pharmaceuticals and by the Bologna Ethical Committee. After informed consent was signed, 17 patients (M/F: 8/9) have been treated with Ponatinib (45 mg orally, once daily) between February 2012 and July 2013, including 14 Ph+ ALL (10 p190, 4 p210) and 3 blast phases of CML (2 Myeloid and 1 Lymphoid, p210). The median age of the patients was 64 years (range 23 -77). The median time from diagnosis was 754 days (range 46-2264). All the patients were resistant or intolerant to previous TKIs (median number of previous TKIs: 2; range 1-3). Standard chemotherapy was previously performed in 7/17 patients (41%). Four patients (23%) had previously received allogeneic stem cell transplantation. At the time of enrolment, median Hb, PLTs and WBC values were 10,9 g/dl (range 8.6-13.9), 139000/mmc (range 14000-325000) and 4300/mmc (range 1700-17000), respectively. In 6 out of 17 patients, additional cytogenetic alterations were revealed. Mutational analysis showed the presence of T315I mutation (9 pts), G250E (1 pt), T315I and Y253H (1 pt), T315I and Y253A (1 pt), V299L (1 pt). No mutations were detected in 4 patients. Results The median treatment duration was 139 days (range 14-540+). Causes of treatment stop were: progression disease (5 patients), savage allogenic stem cell transplantation (6 patients), drug intolerance (1 patient), consisting in grade III headache. With a median follow up of 284 days (range 8-540+), a maHR was obtained in 13/17 patients (76%). After one month of treatment, a reduction of BCR-ABL fusion transcript level was observed in 9/15 patients (60%). For two patients the follow up is too short to be evaluable. The level became undetectable in 4 patients (3 presenting with T315I mutation). After treatment, T315I mutation disappeared in 6 out of the 9 patients who showed this molecular alteration at the beginning of therapy. At the time of this report, 6/17 patients are still on study (35%). Five patients died due to progression disease. As expected, the drug was well tolerated. Non-hematologic adverse events were described in 7/17 patients (grade >III skin rash in 3 patients; grade>II serum lipase increase in 2 patients; grade>II myalgia in 1 patient; grade III headache). Conclusion In our experience, the activity of Ponatinib in advanced Ph+ leukemias, mainly in T315I mutated patients, was confirmed. No treatment-related deaths occurred. The understanding of molecular mechanisms responsible for resistance or lack of response to the drug will be necessary in order to identify patients early on who could take advantage of this treatment. Acknowledgments Work supported by European LeukemiaNet, AIRC, PRIN 2010-2011, University of Bologna and BolognAIL. Disclosures: Soverini: Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; ARIAD: Consultancy. Martinelli:NOVARTIS: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; PFIZER: Consultancy; ARIAD: Consultancy.

scholarly journals Engraftment of Donor Cells after Allogeneic Stem Cell Transplantation: Comparison and Impact of Chimerism in Whole Blood and Peripheral CD3+ T-Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5866-5866
Author(s):  
Yannick Le Bris ◽  
Berger Florian ◽  
Audrey Menard ◽  
Thierry Guillaume ◽  
Pierre Peterlin ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Whole Blood ◽  
Mixed Chimerism ◽  
Post Transplant

Abstract Introduction: After allogeneic stem cell transplantation (allo-SCT), engraftment can be assessed by quantitative polymerase chain reaction (qPCR) using differing donor/recipient markers (Alizadeh et al. Blood, 2002), identified in peripheral blood DNA cells before transplant. We report here on the concomitant examination of the proportions of donor and recipient DNA in peripheral whole blood (WB) and sorted CD3+ T-cells on days +60 and +90, looking at their impact on survival. Patients, material and methods: This monocentric study evaluated the impact on outcomes of early WB and sorted CD3+ T cells chimerism independently and of the four possible combinations of chimerism between WB and sorted CD3+ T-cells. All follow-up chimerism samples from allo-SCT patients performed in adults at Nantes University Hospital between October 2009 and October 2016 were reviewed, focusing on those where both PB and/or CD3+ T-cells were evaluated on days +60 (45-75) and/or +90 (75-120) after allo-SCT. A global cohort of 229 patients (239 grafts) was retrieved, which includes 52 patients evaluable on day +60 only, 67 evaluable on day +90 only and 120 evaluable on both days +60 and +90. A threshold of >95% donor DNA was considered for complete chimerism. Disease free survival (DFS) was calculated from the date of graft until relapse, death or last follow-up. Overall survival (OS) was calculated from the date of graft until death or last follow-up. Chi square tests were used to compare incidences. Log rang test and Kaplan Meier were used to evaluate DFS and OS. Results: The whole cohort comprised 62% males and had a median age of 58 years old (20-74) at the time of allo-SCT. Patients were treated for myeloid-lineage disease in 59% of the cases. Reduced-intensity conditioning was used in 89% (n=212), donors were familial in 45% (n=107), registry in 48% (n=114). Unrelated cord blood units were used in 8% of the cases (n=18). Post-transplant cyclophosphamide (PTCY) was performed in 48 procedures including 33 and 15 with haplo (HG) and matched donors respectively. Considering the 239 allograft procedures, the median follow-up was 5.8 years (95% CI: 3.1-5.8), the rate of relapse 27% and the rate of death 31%. Complete WB chimerism was observed for 80% and 71% of the cases on day +60 and day +90 respectively. Complete CD3+ chimerism was present for 53% and 51% of the grafts at days +30 and +90 respectively. Thus, cases displaying both complete WB and CD3+ chimerism on days +60 and +90 were 53% and 51% respectively, while 27% and 20% were documented with full WB and mixed CD3+ chimerism on days +60 and +90. Mixed chimerism was observed in both WB and CD3+ cells in 14% of the cases on day +60 and 22% on day +90. Finally, a small proportion of patients (6% and 7% at days +60 and +90) displayed an intriguing complete chimerism in CD3+ cells yet mixed WB chimerism. None of these features appeared associated to disease lineage (lymphoid or myeloid) nor cord blood allo-SCT. Interestingly, of the 27 grafts with myeloablative conditioning, only 14 had full WB/CD3+ engraftment on day +60 or +90, and thus all 27 were retained for the study. None of the four WB/CD3 chimerism combinations at the two times considered had an impact on DFS in this cohort. Surprisingly, although full or mixed WB chimerism had no impact on DFS and OS at days +60 and +90, the presence of a mixed CD3+ chimerism (vs full) at day+90 was associated with a significantly better OS (median: 5.8 months years [95%CI: -not reached] versus 3.1 years [95%CI: 2.2- 3.1]; p=0.025). CD3+ chimerism at day+60 has no impact on OS. All HG resulted in full CD3+ chimerism at both time points compared to non HG (100% vs 52%, p<0.0001). The same was almost true when considering PTCY procedures: 90% at day+60 and 92% at day +90. Of note, there was no influence on DFS nor OS of WB or CD3+ chimerism status when considering only HG or PTCY grafts vs others in this series. Discussion: In this large series, early WB chimerism status did not predict outcome. Surprisingly, mixed CD3+ chimerism at day+90 appears to be significantly associated with a longer OS, suggesting that remaining recipient memory lymphocytes could be beneficial. This result has to be confirmed prospectively. It remains also to define the place of donor lymphocyte infusions (DLI) to prevent relapse in patients with full or mixed CD3+ chimerism post-transplant (analyses of DLI received in our patients are on-going). Disclosures Moreau: Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria.

Donor Lymphocyte Infusions to Prevent Relapse in Acute Leukemias after Allogenic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1642-1642
Author(s):  
Christoph Lutz ◽  
Marion Nagy ◽  
Ingo Tamm ◽  
Stefan Neuburger ◽  
Bernd Doerken ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Mixed Chimerism ◽  
Allogenic Stem Cell Transplantation ◽  
Leukemic Relapse ◽  
Chimerism Analysis ◽  
Donor Lymphocyte Infusions

Abstract Purpose: 115 patients with acute lymphoblastic (n = 56) and myeloid leukemia (n = 59) underwent allogenic stem cell transplantation (SCT) from HLA-matched related or unrelated donors between 1998 and 2003. 52/115 patients (45 %) received donor lymphocyte infusions (DLI) for prophylaxis or treatment of relapse after SCT. Subject of this study was to assess efficacy and toxicity of DLI in these patients. Methods: 83/115 patients were transplanted after standard high-dose radio- and chemotherapy (standard SCT) and 32/115 after reduced intensity conditioning (RIC) with fludarabine, busulfan and ATG. 47/115 patients were in CR-1, 22/115 were in CR-2 and 46/115 patients had advanced stages at the time of transplant. DLI were given to 52 patients, 17/52 patients after RIC and 35/52 patients after standard SCT. Indications for DLI were 1. prophylaxis of relapse in 40/52 patients either after RIC (n = 14) or in high-risk leukemias after standard SCT (n = 26; Ph+ ALL in CR-1, AML and ALL > CR-1) and 2. treatment of hematologic relapse in 12/52 patients. DLI were given in escalating doses every 4 weeks. Chimerism analysis of leukocyte subpopulations were performed before and after DLI by multiplex PCR. Patients with refractory leukemia or those who died before day 60 after SCT were not included in this analysis. Results: 52/115 patients received 103 DLI with a median of 2.7 x 107 CD3+ cells/kg. 29/52 patients (56 %) are alive with a median follow-up of 22 months (range 3 – 69 months); 24 (46 %) are in CR and 5 (10 %) are alive in relapse. The 3 year-probability of overall survival (OS) for all patients treated with DLI is 53 % versus 66 % for patients not treated with DLI (not significant). Patients with ALL treated with DLI have a 3 year probability of overall survival (OS) of 68 % versus 46 % for ALL-patients, who did not receive DLI (p=0.03). For patients with AML, 3 year probability of OS is 41% after DLI versus 78% for patients not treated with DLI (p=0.03). The differences in patients with AML can probably be attributed to the fact that 55 % of those receiving DLI were transplanted in relapse compared to only 30 % of those not receiving DLI. In ALL patients equal number of patients were transplanted in relapse (DLI: 43%; no DLI: 38%). 35/49 patients with available chimerism analysis had mixed chimerism before 1. DLI. After DLI 16/30 patients (53 %) with available analysis had converted to full donor chimerism. All patients who received DLI for leukemic relapse died due to disease progression. 34/52 patients (65 %) developed acute GVHD after administration of DLI, with 7/52 patients (13 %) having grade III/IV. Conclusions: In retrospective analysis DLI seem to be an effective treatment strategy with acceptable toxicity to prevent relapse in high-risk leukemias. To monitor the effect of prophylactic DLI Chimerism analysis is a valuable tool. Patients transplanted with advanced disease have a very high relapse risk independent of the administration of DLI. DLI are not suited to treat leukemic relapse.

scholarly journals Superiority of Allogenic Stem Cell Transplantation after Anti-PD1 Therapy over Anti-PD1 Monotherapy Alone in Relapse/Refractory Hodgkin Lymphoma: Real World Evidence from the French Early Access Program

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1638-1638
Author(s):  
Guillaume Manson ◽  
Jean-Baptiste Mear ◽  
Charles Herbaux ◽  
Jean Marc Schiano de Collela ◽  
Rene-Olivier Casasnovas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Allogenic Stem Cell Transplantation ◽  
Free Survival ◽  
Early Access ◽  
Access Program ◽  
Disease Free ◽  
Steroid Refractory

Abstract Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/R) Hodgkin lymphoma (HL). However, long term efficacy and the need for a consolidation with allogenic stem cell transplantation remain unclear. Patient and method: We retrospectively analyzed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcome according to subsequent alloHSCT. Results: After a median follow-up of 31.5 months, the best overall response rate was 64%, including 37.3% complete response (CR). The median progression-free survival (PFS) was 12.1 months and median overall survival (OS) was not reached. At 3 years, PFS and OS rates were 35% and 65%, respectively. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a PR (median = not reached vs 10.1 months). In our cohort, 17 patients underwent consolidation with allogenic stem cells transplantation (alloHSCT) after nivolumab therapy (Figure 1). At the time of transplantation, 8 patients were in CR, 5 in partial response (PR) and 4 had progressed of whom 3 received a salvage therapy before alloHSCT. Interestingly, 6 out of 7 patients who were not in CR at the time of transplantation (5 PR and 1 progressive disease) converted into a CR after alloHSCT. At the time of analysis, 14 patients were alive and 13 remained disease-free after a median follow-up of 30.4 months. One-year OS and PFS from alloHSCT were 82% and 76%, respectively. Among responding patients (i.e. in CR or PR) after nivolumab monotherapy, those who underwent subsequent alloHSCT (N=13) had a better outcome than those who were not consolidated with alloHSCT (N=35) (Figure 2). In the transplanted group, none of the patients relapsed whereas in the non-transplanted group 60% of the patients relapsed (p<0.001). In the transplanted group, all patients experienced graft-versus-host disease (GVHD), acute (N=14) and/or chronic (N=7) GVHD, including 7 patients with grade III-IV GVHD. At the time of analysis, GVHD had resolved in 9 out of 13 patients. Two patients experienced non-infectious febrile syndrome which resolved with corticosteroids and one patient experienced a sinusoidal obstructive syndrome. Two patients died, one from steroid-refractory GVHD and encephalitis, one from unexplained hemoptysis after experienced steroid-refractory GVHD. Conclusions: Although patients who achieve a CR upon anti-PD1 therapy may experience prolonged remissions, most R/R HL patients treated with anti-PD1 antibody eventually progress or relapse. Our study demonstrates unprecedented disease-free survival in patients undergoing consolidation with alloHSCT after anti-PD1 therapy. Interestingly, alloHSCT post anti-PD1 can convert incomplete responses into CR in most cases. Despite expected toxicities, alloHSCT after anti-PD1 therapy appears manageable and safe in most patients. Our results suggest that consolidation with alloHSCT may represent a good option in patients treated with anti-PD1, notably in patients who are unable to achieve a CR. Disclosures Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Stamatoullas:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Consultancy. Brice:bristol myers squibb: Consultancy, Honoraria. Houot:bristol myers squibb: Consultancy, Honoraria.

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