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Hemophagocytic lymphohistiocytosis (HLH) may be secondary to cancer or other conditions in adults. We aimed to compare characteristics and outcomes of secondary HLH depending on cancer status among adults. Weight loss over 10 %, headache and enlarged lymph nodes were more frequent in malignant- HLH (M-HLH). Higher phosphatase alkaline level and CRP level were present in M-HLH. Mortality rate tended to be higher in M-HLH group in the first month and during the two years follow-up. Some clinical features and biological abnormalities are associated with an increased probability of malignancy in secondary HLH among adults.

Purpose: To evaluate CD4+ helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT).Experimental Design: To evaluate the widespread immunogenicity of UCPs in humans, spontaneous T-cell responses against UCPs were measured in various types of cancers using T-cell proliferation and ELISPOT assays. The humanized HLA-DRB1*0101/HLA-A*0201 transgenic mice were used to study the CD4+ helper effects of UCPs on antitumor CTL responses. UCP-based antitumor therapeutic vaccine was evaluated using HLA-A*0201–positive B16 melanoma that express TERT.Results: The presence of a high number of UCP-specific CD4+ T cells was found in the blood of patients with various types of cancer. These UCP-specific T cells mainly produce IFN-γ and TNF-α. In HLA transgenic mice, UCP vaccinations induced high avidity CD4+ TH1 cells and activated dendritic cells that produced interleukin-12. UCP-based vaccination breaks self-tolerance against TERT and enhances primary and memory CTL responses. Furthermore, the use of UCP strongly improves the efficacy of therapeutic vaccination against established B16-HLA-A*0201 melanoma and promotes tumor infiltration by TERT-specific CD8+ T cells.Conclusions: Our results showed that UCP-based vaccinations strongly stimulate antitumor immune responses and could be used to design efficient immunotherapies in multiple types of cancers. Clin Cancer Res; 18(22); 6284–95. ©2012 AACR.

Additonnal data (Material & Method)

PDF file - 57K, UCPs mediated helper effect on CTLs in other models of vaccinations

Figure S1. In vitro detection (using #A3C3) of recombinant IL-1RAP protein by ELISA Figure S2. Procedure for generating IL-1RAP CART cells and CD4/CD8 ratio at the end of the process Figure S3. Staining of IL-1RAP CAR at the cell surface of T cell line or primary T -lymphocytes Figure S4. Impact of the IL-1RAP soluble form on IL-1RAP CART-cells toxicity Figure S5. Tissue macroarray (TMA) using #A3C3 monoclonal antibody Figure S6. Experimental immunosafety human CD34+ engrafted NOG murine model Figure S7. Colony Forming Unit (CFU-GM) experiment after coculture of autologous CART-cells with CD34+ HSC. Figure S8. In-vitro and in-vivo iCASP/AP1903 suicide gene safety switch Figure S9. Production and characterization of IL-1RAP (soluble and membrane) transfected cell line Figure S10. Cytokine secretion profiling of IL-1RAP CART-cells after co-culturing with targets Figure S11. Tumoral xenograft murine model Figure S12. Autologous cytotoxicity of IL-1RAP CART-cells directed against initial CML disease Table S1: Antibodies and kits Table S2: IL-1RAP (mAb#A3C3) immunostaining of normal tissues Table S3: Percentage of alive cells in different subpopulations according co-culture with different ratio of E (MockT-cells or IL-1RAP CART-cells) :T. Table S4: CML patient's characteristics with available PBSC cryopreserved autografts

PDF file - 65K, UCP2 and UCP4 peptides increase self/TERT pY572 specific CTL responses

PDF file - 26K, UCP2 specific CD4 T cells recognize the mTERT-derived counterpart peptide p568

Figure S1. In vitro detection (using #A3C3) of recombinant IL-1RAP protein by ELISA Figure S2. Procedure for generating IL-1RAP CART cells and CD4/CD8 ratio at the end of the process Figure S3. Staining of IL-1RAP CAR at the cell surface of T cell line or primary T -lymphocytes Figure S4. Impact of the IL-1RAP soluble form on IL-1RAP CART-cells toxicity Figure S5. Tissue macroarray (TMA) using #A3C3 monoclonal antibody Figure S6. Experimental immunosafety human CD34+ engrafted NOG murine model Figure S7. Colony Forming Unit (CFU-GM) experiment after coculture of autologous CART-cells with CD34+ HSC. Figure S8. In-vitro and in-vivo iCASP/AP1903 suicide gene safety switch Figure S9. Production and characterization of IL-1RAP (soluble and membrane) transfected cell line Figure S10. Cytokine secretion profiling of IL-1RAP CART-cells after co-culturing with targets Figure S11. Tumoral xenograft murine model Figure S12. Autologous cytotoxicity of IL-1RAP CART-cells directed against initial CML disease

Chronic myeloid leukemia (CML) is a chronic disease resulting in myeloid cell expansion through expression of the BCR-ABL1 fusion transcript. Tyrosine kinase inhibitors (TKI) have significantly increased survival of patients with CML, and deep responders may consider stopping the treatment. However, more than 50% of patients relapse and restart TKI, subsequently suffering unknown toxicity. Because CML is a model immune system–sensitive disease, we hypothesize that chimeric antigen receptor (CAR) T cells targeting IL1 receptor-associated protein (IL1RAP) in quiescent CML stem cells may offer an opportunity for a permanent cure. In this study, we produced and molecularly characterized a specific monoclonal anti-IL1RAP antibody from which fragment antigen-binding nucleotide coding sequences were cloned as a single chain into a lentiviral backbone and secured with the suicide gene iCASP9/rimiducid system. Our CAR T-cell therapy exhibited cytotoxicity against both leukemic stem cells and, to a lesser extent, monocytes expressing IL1RAP, with no apparent effect on the hematopoietic system, including CD34+ stem cells. This suggests IL1RAP as a tumor-associated antigen for immunotherapy cell targeting. IL1RAP CAR T cells were activated in the presence of IL1RAP+ cell lines or primary CML cells, resulting in secretion of proinflammatory cytokines and specifically killing in vitro and in a xenograft murine model. Overall, we demonstrate the proof of concept of a CAR T-cell immunotherapy approach in the context of CML that is applicable for young patients and primary TKI-resistant, intolerant, or allograft candidate patients.Significance:These findings present the first characterization and proof of concept of a chimeric antigen receptor directed against IL1RAP expressed by leukemic stem cells in the context of CML.

PDF file - 51K, Isolation of UCP4-specific CD4 Th1 cell clone from a cancer patient

PDF file - 38K, Comparison of T-cell help mediated by UCP2 and a HTLV-1 Tax-derived peptide on self/TERT pY988 specific CTL response

In single unrelated cord blood transplantation (UCBT), an increasing number of HLA allele mismatches (MM) has been associated with inferior overall survival (OS) attributed to higher transplant-related mortali-ty (TRM). Previous studies on the role of allele-level HLA matching following double UCBT (dUCBT) showed conflicting results. Herein we report the impact of allele-level HLA matching on outcomes of a large dUCBT cohort . We included 963 adults with hematologic malignancies, with available allele-level HLA matching at HLA-A, -B, -C and -DRB1, receiving dUCBT between 2006-2019. Assignment of donor-recipient HLA match was performed considering the unit with the highest disparity with the recipient. 392 patients received dUCBT with 0-3 and 571 with ≥4 allele MM. Day-100 and 4-year TRM were 10% and 23%, for recipients of dUCBT with 0-3 MM compared to 16% and 36% for those with ≥4 MM (HR 1.58, p=.002; and HR 1.54, p=.002), respectively. Higher degree of allele MM was also associated with worse neutrophil recovery and lower incidence of relapse; no significant effect on graft-versus-host disease was observed. Patients receiving units with 0-3 MM had a 4-year OS of 54% versus 43% for those with ≥4 MM (HR 1.40, p=.005). The inferior OS associated with higher HLA disparity was only partially mitigated by increased total nucleated cell doses. Our results confirm that allele-level HLA typing is a significant factor for OS following dUCBT and units with ≥4 MM (≤4/8 HLA-matched) should be avoided if possible.

We report the results from a multicentre retrospective study of 220 adult patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) for therapy-related acute myeloid leukemia (t-AML). Median age at t-AML diagnosis was 56 years, with a prior history of haematological (45%) or gynaecological neoplasia (37%). Median time from cytotoxic exposure to t-AML diagnosis was 54.7 months. At transplant, around 20% of patients had measurable residual disease and 3% of patients were not in complete remission. The median follow-up was 21.4 months (Q1-Q3, 5.9–52.8). At 12 months, overall survival (OS), event-free survival (EFS), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS) were 60.7% (95% CI 54.6–67.5), 52.8% (95% CI 46.5–68.4), and 44.1% (95% CI 37.6–51.8), respectively. At 5 years, OS, EFS, and GRFS were 44.1% (95% CI 37.4–52.1), 40.4% (95% CI 33.9–48.1), and 35.3% (95% CI 28.8–43.3), respectively. At last follow-up, 44% of patients were in complete remission (n = 96) and transplant-related mortality accounted for 39% of all deaths (n = 119). Multivariable analysis revealed that uncontrolled t-AML at transplant was associated with lower EFS (HR 1.94, 95% CI 1.0-3.7, p = 0.041). In conclusion, alloHSCT for t-AML shows encouraging results and offers additional opportunity with the emergence of novel pre-graft therapies.

Acute graft-versus-host disease (aGVHD) is a major limitation of the therapeutic potential of allogeneic hematopoietic cell transplantation. Lipopolysaccharides (LPS) derived from intestinal gram-negative bacteria are well-known aGVHD triggers and amplifiers. Here, we explored the LPS metabolism in aGVHD mouse models using an innovative quantification method. We demonstrated that systemic LPS accumulation after transplantation was due, at least partly, to a defect in its clearance through lipoprotein-mediated transport to the liver (i.e., the so-called reverse LPS transport). After transplantation, reduced circulating HDL concentration impaired LPS neutralization and elimination through biliary flux. Accordingly, HDL-deficient (Apoa1

International audience; BackgroundAllogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome . We retrospectively compared patient outcomes after allo-HSCT according to the intensity of the conditioning regimen.Patients and MethodsThree conditioning regimens were compared in 427 patients allografted for high-risk myelodysplastic syndrome: reduced-intensity conditioning (RIC), fludarabine (150-160 mg/m2) and busulfan (6.4 mg/kg); sequential FLAMSA-RIC, fludarabine, amsacrine, and aracytine followed by RIC; and myeloablative with reduced toxicity (RTC), fludarabine and busulfan (9.6 mg/kg or 12.8 mg/kg).ResultsThe patients in the 3 conditioning groups were different in regards to the number of treatment lines (P< .001), percentage of blasts in bone marrow (P< .001), and disease status at transplantation (P< .001). No significant differences in outcomes (overall survival, progression-free survival, nonrelapse mortality, relapse incidence, and graft versus host disease relapse-free survival) were observed between the 3 groups. Using propensity score analysis to overcome baseline imbalances, we compared 70 patients receiving FLAMSA-RIC to 260 patients receiving RIC, and compared 83 patients receiving RTC to 252 patients receiving RIC. The only factor influencing overall and progression-free survival was cytogenetic risk at transplantation. After the covariate adjustment using propensity score to reduce baseline imbalances, the only factor influencing overall and progression-free survival was still cytogenetic risk at transplantation.ConclusionOverall survival appears to be similar with the 3 conditioning regimens. The only factor influencing survival is cytogenetic risk at transplantation, suggesting that new promising drugs in the conditioning and/or early interventions after transplantation are needed to improve outcomes in these patients.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Unfortunately, it is still associated with a significant risk of relapse due to mechanisms of escape from the control of alloreactive T cells. Repetitive adjuvant donor lymphocyte infusions (DLI), termed prophylactic DLI (proDLI), as an effective strategy in preventing relapse is still debated. Methods: We performed a retrospective multicenter study to evaluate the efficacy of proDLI in allografted AML and MDS. We identified 56 patients treated with proDLI (DLI planned in full chimeras without any sign of disease relapse) and matched them to 167 patients in control group, (DLI performed for mixed chimerism or positive minimal residual disease) based on similar age, initial disease, cytogenetic prognosis, and conditioning intensity. Results: In univariate analysis, the incidence of severe aGVHD at 100 days and incidence of all grades of chronic GVHD 1 year after allo-HSCT were similar in the two groups. We also observed a trend of higher 3-year RI (52.61% [95% confidence interval 25.99-79.23]) in the proDLI group versus the control group (29.31% [20.28-38.34], p=0.067). However, 3-year overall survival (p=0.892), progression-free survival (p=0.239), and non-relapse mortality (p=0.343) were similar between the two groups. In multivariate analysis, the only factor influencing overall and progression-free survival was anti-thymocyte globulin administration during the conditioning regimen. Discussion/Conclusion: The proDLI strategy had an acceptable toxicity profile but did not improve patient outcomes compared to the pre-emptive strategy.

BackgroundAcute myeloid leukemia (AML) remains a very difficult disease to cure due to the persistence of leukemic stem cells (LSCs), which are resistant to different lines of chemotherapy and are the basis of refractory/relapsed (R/R) disease in 80% of patients with AML not receiving allogeneic transplantation.MethodsIn this study, we showed that the interleukin-1 receptor accessory protein (IL-1RAP) protein is overexpressed on the cell surface of LSCs in all subtypes of AML and confirmed it as an interesting and promising target in AML compared with the most common potential AML targets, since it is not expressed by the normal hematopoietic stem cell. After establishing the proof of concept for the efficacy of chimeric antigen receptor (CAR) T-cells targeting IL-1RAP in chronic myeloid leukemia, we hypothesized that third-generation IL-1RAP CAR T-cells could eliminate AML LSCs, where the medical need is not covered.ResultsWe first demonstrated that IL-1RAP CAR T-cells can be produced from AML T-cells at the time of diagnosis and at relapse. In vitro and in vivo, we showed the effectiveness of IL-1RAP CAR T-cells against AML cell lines expressing different levels of IL-1RAP and the cytotoxicity of autologous IL-1RAP CAR T-cells against primary cells from patients with AML at diagnosis or at relapse. In patient-derived relapsed AML xenograft models, we confirmed that IL-1RAP CAR T-cells are able to circulate in peripheral blood and to migrate in the bone marrow and spleen, are cytotoxic against primary AML cells and increased overall survival.ConclusionIn conclusion, our preclinical results suggest that IL-1RAP CAR T-based adoptive therapy could be a promising strategy in AML treatment and it warrants the clinical investigation of this CAR T-cell therapy.

International audience; Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow-up of 191 days (3–260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.

Oncogenesis and ontogeny of blastic plasmacytoid dendritic cell neoplasm (BPDCN) remain uncertain, between canonical plasmacytoid dendritic cells (pDCs) and AXL+ SIGLEC6+ DCs (AS-DCs). We compared 12 BPDCN to 164 acute leukemia by Affymetrix HG-U133 Plus 2.0 arrays: BPDCN were closer to B-cell acute lymphoblastic leukemia (ALL), with enrichment in pDC, B-cell signatures, vesicular transport, deubiquitination pathways, and AS-DC signatures, but only in some cases. Importantly, 1 T-cell ALL clustered with BPDCN, with compatible morphology, immunophenotype (cCD3+ sCD3− CD123+ cTCL1+ CD304+), and genetics. Many oncogenetic pathways are deregulated in BPDCN compared with normal pDC, such as cell-cycle kinases, and importantly, the transcription factor SOX4, involved in B ontogeny, pDC ontogeny, and cancer cell invasion. High-throughput sequencing (HaloPlex) showed myeloid mutations (TET2, 62%; ASXL1, 46%; ZRSR2, 31%) associated with lymphoid mutations (IKZF1), whereas single-nucleotide polymorphism (SNP) array (Affymetrix SNP array 6.0) revealed frequent losses (mean: 9 per patient) involving key hematological oncogenes (RB1, IKZF1/2/3, ETV6, NR3C1, CDKN2A/B, TP53) and immune response genes (IFNGR, TGFB, CLEC4C, IFNA cluster). Various markers suggest an AS-DC origin, but not in all patients, and some of these abnormalities are related to the leukemogenesis process, such as the 9p deletion, leading to decreased expression of genes encoding type I interferons. In addition, the AS-DC profile is only found in a subgroup of patients. Overall, the cellular ontogenic origin of BPDCN remains to be characterized, and these results highlight the heterogeneity of BPDCN, with a risk of a diagnostic trap.

International audience; No abstract available

Background. Use of haploidentical cell transplantation (Haplo-HCT) with peripheral blood stem cells (PBSC) is increasing for acute myeloid leukemia (AML). We explored whether the addition of antithymocyte globulin (ATG) to post-transplant cyclophosphamide (PTCy) allows better outcomes than PTCy alone in Haplo-PBSC.Methods. We included 441 adult patients undergoing a first Haplo-PBSC for AML in first or second complete remission; graft-versus-host disease (GVHD) prophylaxis contained either PTCy alone (n = 374) or ATG + PTCy (n = 67), in addition to cyclosporine A (CsA) and mycophenolate mofetil (MMF) as other immunosuppressive agents. Transplant period was 2011–2019.Results. No major imbalances were observed between the two groups. Median age was 56 years and median year of Haplo-HCT was 2017 for both groups. Most patients received a reduced-intensity conditioning regimen (57% and 61% in PTCy and ATG + PTCy, respectively; p = 0.54). Median follow-up was 19 versus 15 months in PTCy and ATG + PTCy, respectively (p = 0.59). Neutrophil engraftment occurred in 97% and 98% of PTCy and ATG + PTCy, respectively. In univariate analysis, no statistical differences in transplant outcomes were observed between PTCy and ATG + PTCy. In multivariate analysis ATG + PTCy resulted in a lower risk of chronic GVHD as compared to PTCy alone (HR = 0.46, 95% CI 0.23–0.93; p = 0.03). No differences were observed for the other transplant outcomes.Conclusion. In Haplo-PBSC, addition of ATG to PTCy (with CsA and MMF) is feasible, better at preventing chronic GVHD, and survival and transplant outcomes are comparable to those with PTCy alone, without increasing transplant toxicity, mortality, or relapse incidence.

The impact of acute graft versus host disease (GVHD) on survivals for patients receiving a haploidentical allogeneic stem-cell transplant (Allo-SCT) with peripheral blood stem-cells (PBSC) complemented by post-transplant cyclophosphamide (PTCY) is ill-known.This retrospective study included 131 patients who received a PBSC haplograft in order to precise the impact of acute GVHD on outcomes. There were 78 males and 53 females and the median age for the whole cohort was 59 years (range: 20-71). Thirty-five patients were allografted for a lymphoid disease and 96 for a myeloid malignancy, including 67 patients with acute myeloid leukemia (AML).The cumulative incidence (CI) of day 100 grade 2-4 and 3-4 acute GVHD was 43.4 + 4.6% and 16.7 + 3.4%, respectively. The 2-year CI of moderate/severe chronic GVHD was 10.1 + 2.8%. The only factor affecting the occurrence of GVHD was GVHD prophylaxis. Indeed, CI of day 100 grade 2-4 (but not grade 3-4) acute GVHD was significantly reduced when adding anti-thymoglobulin (ATG) to PTCY. However, in multivariate analysis, grade 2 acute GVHD was significantly associated with better disease-free (HR: 0.36; 95%CI: 0.19-0.69,Acute grade 2 GVHD is a factor of good prognosis after PBSC haplotransplant with PTCY. Further and larger studies are needed to clarify the complex question of GVHD prophylaxis in the setting of haplo-transplant, especially that of combining ATG and PTCY.

Introduction: Cellular composition of grafts is believed to be one of the significant determinants of outcomes of reduced-intensity conditioning (RIC) allogenic hematopoietic cell transplantation (allo-HCT). However, inconsistent results of the influence of CD34+ cells dose on the incidence of graft-versus-host disease (GVHD), disease control and survival have been reported in studies published thus far. Allo-HCT remains the only potentially curative treatment modality for eligible patients with myelofibrosis (MF). As patients with this diagnosis were underrepresented or not included in the above mentioned analyses, this EBMT registry study aimed to determine impact of CD34+ cell counts on allo-HCT results in this population. Methods: Six hundred and fifty seven patients with primary or secondary MF transplanted with use of peripheral blood (PB) as a source of stem cells after RIC regimen (Fludarabine/Melphalan, N=536 (82%); Fludarabine/Busulphan, N=121 (18%)) between 2000 and 2016 were included. Stem cell donor type was HLA-identical sibling (MSD; N=249, 38%) or unrelated (UD; N=408, 62%). Use of ex vivo T-cell depletion and post-transplant cyclophosphamide to prevent GVHD were the exclusion criteria. Median patient age was 58 (range, 22-76) years. In-vivo T-cell depletion was used in 526 (80%) of cases. Median transplanted CD34+ dose was 6.6 (2-29) x 10^6 per kg of recipient body weight. Median follow-up was 46 (2-194) months. Patient and transplant characteristics are summarized in Table 1. Results: We did not observe any impact of CD34+ cells dose on outcome variables in the whole study group. However, in an analysis adjusted for donor type, among patients transplanted from a MSD, the 2yr overall survival (OS) probability was 77% for those transplanted with higher doses of CD34+ cells (defined as >7.0 x 10^6/kg) compared to 60% for lower CD34+ counts (below 7.0 x 10^6/kg), P=0.007 (Figure 1). The corresponding probabilities of 2yr non-relapse mortality (NRM) were 16% and 29% (P=0.04), respectively (Figure 2). In multivariate analysis, for patients transplanted from a MSD, higher CD34+ dose was an independent predictor for better survival (HR 0.56; P=0.01) and lower risk of NRM (HR 0.54; P=0.02). We did not find any association between CD34+ counts with probability of engraftment, the incidence of acute (aGVHD) and chronic (cGVHD) nor disease relapse. The effect of cell dose was not seen in the UD cohort. Factors associated independently with an unfavorable outcome in the whole study group were: older patient age and transplantation from CMV seronegative donors to seropositive recipients for OS and NRM and use of an UD and female donor for NRM. Allo-HCT from UD was also an independent predictor for higher incidence of aGVHD and lower probability of engraftment. Use of in vivo T-cell depletion was a protective factor for aGVHD. It was in turn associated with higher risk of relapse. Conclusions: Our analysis suggests a potential survival benefit for MF patients treated with RIC PB-allo-HCT from MSD with higher doses of CD34+ cells (threshold > 7.0 x 10^6/kg). We suggest that this factor should be taken into consideration when planning and performing hematopoietic cell apheresis. Disclosures Kröger: Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Robin:Novartis Neovii: Research Funding. Chevallier:Daiichi Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria. Mielke:Bellicum: Consultancy, Honoraria, Other: Travel (via institution); EBMT/EHA: Other: Travel support; Miltenyi: Consultancy, Honoraria, Other: Travel and speakers fee (via institution), Speakers Bureau; IACH: Other: Travel support; Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau; ISCT: Other: Travel support; GILEAD: Consultancy, Honoraria, Other: travel (via institution), Speakers Bureau; Celgene: Honoraria, Other: Travel support (via institution), Speakers Bureau; DGHO: Other: Travel support; Kiadis Pharma: Consultancy, Honoraria, Other: Travel support (via institution), Speakers Bureau. Snowden:Janssen: Honoraria; Mallinckrodt: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; IDMC: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Blaise:Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria. Hernandez Boluda:Incyte: Other: Travel expenses paid. McLornan:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria.

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for patients with myeloid/lymphoid neoplasm (MLN) with FGFR1 rearrangement, but data on overall results are limited. We report on the largest series of patients (n = 22) with FGFR1-rearranged MLN undergoing allo-HCT. Distribution according to cytogenetic subtype was: t(8;13) in 11 cases, t(8;22) in 7 cases, t(6;8) in 2 cases, and other (n = 2). Over a third of patients displayed a chronic myeloproliferative (MPN) phenotype, another third showed MPN features with concomitant lymphoma or acute leukemia, and the remaining ones presented as acute leukemia. After a median follow-up of 4.1 years from transplant, the estimated 5-year survival rate, progression-free survival, non-relapse mortality and relapse incidence was 74%, 63%, 14% and 23%, respectively. Causes of death were relapse/progression (n = 4), graft-versus-host disease (n = 2) and organ toxicity (n = 1). Six patients experienced disease relapse at a median of 6.1 months (range: 2.3-119.6). Two of them achieved complete remission with ponatinib or pemigatinib and were alive at 34.5 and 37 months from relapse, respectively. These data highlight the significant curative potential of allo-HCT in this aggressive disease. Maintenance with tyrosine kinase inhibitors may be a promising approach, at least in cases with detectable residual disease after transplant.

The use of haploidentical hematopoietic cell transplantation (haplo-HCT) with peripheral blood stem cells (PBSCs) to treat acute myelogenous leukemia (AML) is increasing. We explored whether the addition of antithymocyte globulin (ATG) to post-transplantation cyclophosphamide (PTCy) allows better outcomes compared with PTCy alone in haplo-HCT with PBSCs (haplo-PBSCT). We included 441 adult patients undergoing a first haplo-PBSCT for AML in first or second complete remission; graft-versus-host disease (GVHD) prophylaxis contained either PTCy alone (n = 374) or ATG plus PTCy (n = 67), in addition to cyclosporine A (CsA) and mycophenolate mofetil (MMF) as other immunosuppressive agents. All transplantations were performed between 2011 and 2019. No major imbalances were observed between the 2 groups. For both groups, the median patient age was 56 years, and the median year of haplo-PBSCT was 2017. Most patients received a reduced-intensity conditioning regimen (57% in the PTCy group and 61% in the ATG+PTCy group; P = .54). The median follow-up was 19 months in the PTCy group versus 15 months in the ATG+PTCy group (P = .59), and the rate of neutrophil engraftment in the 2 groups was 97% and 98%, respectively. In univariate analysis, there were no statistical differences in transplantation outcomes between the 2 groups. In multivariate analysis, ATG+PTCy was associated with a lower risk of chronic GVHD compared with PTCy alone (hazard ratio, .46; 95% confidence interval, .23 to .93; P = .03). No between-group differences in the other transplantation outcomes were seen. In haplo-PBSCT, the addition of ATG to PTCy (with CsA and MMF) is feasible and better at preventing chronic GVHD and is associated with survival and transplantation outcomes comparable to those with PTCy alone, without increasing transplantation toxicity, mortality, or relapse incidence.

Background Cancer patients are considered highly vulnerable to the COVID-19 pandemic. However, delaying cancer-specific therapies could have a deleterious effect on survival. The potential suppressive effects of chemotherapies or cancer-related microenvironment raised the question on how cancer patients’ immune system responds to SARS-CoV-2 virus. Methods We have started a prospective monocentric trial entitled COV-CREM (NCT04365322) in April 2020. The primary objective of the trial was to assess specific immune response's intensity and diversity to SARS-CoV-2 in infected patients. Results In this study, we showed that cancer patients (28 solid tumours, 11 haematological malignancies) exposed to SARS-CoV-2 produced a high rate of specific antibodies, as observed in patients without a cancer history (n = 29). However, our results highlight a lack in the generation of T-cell responses against CoV–N, M and S proteins from the SARS-CoV-2 virus, suggesting that cancer patients failed to mount a protective T-cell immunity. Nevertheless, SARS-CoV-2 infection did not impair established immune memory since specific responses against common viruses were not hampered in cancer patients. Conclusion Given the severity and the unknown evolution of the ongoing COVID-19 pandemic, it is of fundamental importance to integrate cancer patients in vaccination programs.