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Resume Les complications stomatologiques de l’allogreffe de cellules souches hematopoietiques (CSH) sont frequentes et tres inconfortables pour les patients. La reaction du greffon contre l’hote represente la principale complication. Les infections, les troubles du gout et les risques carcinologiques constituent les autres effets secondaires de la procedure. Differents traitements locaux sont utilises mais restent imparfaits. Dans le cadre de la dixieme edition des ateliers d’harmonisation des pratiques en allogreffe, organises par la Societe francophone de greffe de moelle et de therapie cellulaire (SFGM-TC) a Lille, en septembre 2019, la demarche diagnostique et les traitements des complications orales apres allogreffe de CSH ont ete revus apres analyse des resultats des etudes publiees.

International audience; Acute and chronic renal failures are very common after allogeneic HSCT. These complications have a real impact on mortality and morbidity of transplant recipients. Within the framework of the ninth workshops of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held in Lille in September 2018, various causes and mechanisms of renal failure, diagnostic work-up, treatment and recommendations to limit renal failure after transplantation are reviewed. Recommendations to adjust medications to avoid renal failure are also proposed in this article.

Resume La greffe allogenique de cellules souches hematopoietiques (CSH) est une therapeutique usuelle pour de nombreuses maladies hematologiques. Au cours des dernieres decennies, des progres importants ont ete realises dans les domaines de la prise en charge des patients. La selection des donneurs, les conditionnements de greffe et les soins de support des patients ont contribue a l’amelioration de la survie des patients. La plupart des procedures en rapport avec la greffe allogenique de CSH ont ete standardisees par des recommandations nationales ou internationales amenant a des certifications telles que Joint Accreditation Committee ISCT-Europe & EBMT (JACIE). Mais tous ces standards et ces recommandations ne definissent pas de facon precise les moyens minimums humains et materiels necessaires a la realisation de telles procedures. En plus, les unites dans lesquelles sont places ces patients sont soumises a des regles architecturales et procedurales non uniformisees. Lors de cet atelier, nous avons tente de definir une trame minimale concernant le personnel, l’infrastructure architecturale et des pratiques d’hygiene generales pour les patients, le personnel et les visiteurs.

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (

Allogeneic hematopoietic cell transplantation (allo-HCT), the only curative therapy for numerous hematological malignancies, carries a significant risk of morbidity and mortality. The patients and families’ expectations regarding the procedure, the prognosis uncertainties, as well as the existence of potential new therapeutic possibilities, lead to frequent use of intensive care. Even though the transplant physicians are highly skilled in acute care, their knowledge of palliative approach is limited, making the use of palliative care insufficient and often late. By promoting reflection on the proportionality of care and the patients’ quality of life, palliative care may contribute to the allo-HCT patients management. Nevertheless, obstacles to this approach remain. The objective of this work is to propose recommendations to promote the implementation of palliative care into transplant units., L’allogreffe de cellules hématopoïétiques, seule perspective curative pour certaines hémopathies malignes, comporte des risques de morbi-mortalité importants. Les attentes des patients et de leurs proches vis-à-vis de la procédure, les incertitudes pronostiques, ainsi que l’existence de nouvelles possibilités thérapeutiques, engendrent un recours fréquent, onéreux aux soins intensifs. Si les médecins greffeurs maîtrisent parfaitement les soins actifs, leur connaissance en ce qui concerne les soins palliatifs est limitée, rendant l’accès à ces soins très restreint et souvent tardif. Favorisant une réflexion sur la proportionnalité des soins et sur la qualité de vie des patients, les soins palliatifs peuvent contribuer à la prise en charge des patients allogreffés et à l’accompagnement de leurs proches. Néanmoins, des obstacles à cette approche demeurent. Cet article a pour objectif de proposer des recommandations pour favoriser l’intégration de la démarche palliative au sein des unités d’allogreffe.

Simple Summary Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) initiated a study to better describe COVID-19 presentation and evolution in patients followed in French pediatric oncology and hematology wards. By describing COVID-19 in this specific population, we aimed to identify the patients who may be the most at risk of severe COVID-19 and establish specific recommendations. Abstract Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) initiated a study to better describe COVID-19 in patients followed in French pediatric oncology and hematology wards. All patients diagnosed with COVID-19 and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Data were available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Children and young adults treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored.

Introduction: Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) has initiated a study to better describe the presentation and evolution of COVID-19 in patients followed in French pediatric oncology and hematology wards. Methods: All patients diagnosed with COVID-19 (polymerase chain reaction [PCR] positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], or positive IgM serology, or chest computed tomography scan and clinical signs typical of COVID-19) and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Results: Data was available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Conclusion: Children and young adults infected with SARS-CoV-2 and treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored. (NCT04433871)

Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE...). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins... Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach.

International audience; Minimal residual disease (MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (ALL). Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non-ex vivo T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T-cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high-risk paediatric ALL enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with MRD \textless10(-3) and the 27 with MRD ≥10(-3) . Multivariate analysis identified sex match and MRD as being significantly associated with 5-year survival. MRD ≥10(-3) compromised the 5-year cumulative incidence of relapse (43*6 vs. 16*7%). Complete remission status and stem cell source did not modify the relationship between MRD and prognosis. Thus, pre-transplant MRD is still a major predictor of outcome for ALL. The MRD-guided strategy resulted in survival for 72*3% of patients with MRD\textless10(-3) and 40*4% of those with MRD ≥10(-3).

Abstract 1251 Allogeneic stem cell transplantation (allo-SCT) following reduced-intensity conditioning (RIC) represents a concrete alternative to standard myeloablative conditioning. Even though, immune reactions observed after RIC (i.e. GVHD, GVL.), tend to be similar to those observed after myeloablative regimens, there are many differences in their clinical features, timing of onset, and their impact on patient's outcome. The homeostatic cytokines, IL-7 and IL-15 are essential driving forces for homeostatic peripheral expansion of T lymphocytes that are responsible, not only for GVL effect but also for GVHD which is a major complication post-transplant. Almost all mature T-cells express the specific IL-7 receptor alpha chain (IL-7Rα). Memory CD8+ T cells and natural killer (NK) cells express the highest levels of IL-2/15Rβ chain, making these cells particularly responsive to IL-15. Few studies have associated GVHD with systemic levels of either IL-7 or IL-15 but only one concerned patients undergoing RIC. However, patients reported in the latter study, had received prior induction chemotherapy and experienced profound lymphopenia after conditioning, leading to levels of IL-7 and IL-15 comparable to those usually observed after myeloablative regimens. In addition, the issue of IL-7R and IL-2/15Rβ expression has not been addressed yet in allo-SCT patients. This prompted us to prospectively investigate plasma levels of IL-7 and IL-15, T-cell recovery, and the expression levels of IL-7Rα and IL-2/15Rβ chains in patients undergoing RIC. Forty-five consecutive patients who underwent fully HLA-matched allo-SCT after RIC were included. Plasma levels of IL-7 and IL-15 were determined by ELISA at enrolment, on day 0 before grafting, every three days during the first month, and then on days 60 and 90. CD3+, CD4+, CD8+ T-cells and NK cells counts at day 30, 60 and 90 post-graft were obtained by flow-cytometry-based technique. Expression of IL-7Rα and IL-2/15Rβ (% and MFI) was evaluated on each subsets of naïve and memory T-cells, categorized according to their expression of CD45RA and CCR7 markers. Kinetic courses of plasma IL-7 levels, evolved inversely to lymphocyte counts up to day 30 (R= -.529; P= .001). The higher plasma IL-7 levels were associated with the lower MFI of IL-7Rα on CD4+ naïve, CD8+ naïve, CD4+ central memory, and CD8+ central memory T-cells (p=.005, .01, A total of 16 (35%) recipients developed grades 2–4 acute GVHD (aGVHD) at a median time of 42 days post graft. By day +30, IL-7 and IL-15 levels were slightly correlated with aGVHD grades (R=.30; P=.05 and R=.31; P = .048, respectively) and inversely correlated with the time to onset (IL-7: R= -.334; P= .031 and IL-15: R= -.367; P= .018). In those patients, there was a diminished surface densities of IL-7Rα chain in both the naïve (P= .029) and the central memory (P= .043) CD4+ T-cells. In multivariate analysis, IL-7 level measured on day +30 was the foremost predictive factor for grade 2–4 aGVHD (P= .002). Collectively, this study indicates that the level of IL-7 depends rather on the level of lymphopenia whereas IL-15 is more sensitive to the inflammatory context. A high level of IL-7 induces a downregulation of IL-7Rα on naïve and central memory CD4+ T cells, already known to contain alloreactive T cells. The determination of plasma level of IL-7 by day+30 would help predict aGVHD. This predictive time is less precocious than those observed after myeloablative conditioning in agreement with the later development of aGVHD observed with RIC regimens. Disclosures: No relevant conflicts of interest to declare.

Abstract 2329 The mainstay of treatment for Chronic Graft Versus Host Disease (cGVHD) is steroids, but there are limited treatment options for steroid refractory cGVHD particularly in its sclerotic and fibrotic form (ScGVHD). We initially reported the efficacy and safety of imatinib mesylate (IM), a first generation tyrosine kinas' inhibitor, as a salvage therapy for ScGVHD patients (Magro L, et al. Blood, 2009). However, about 50% of the patients (Pts) became refractory or intolerant to IM. Nilotinib, a second generation tyrosine kinas' inhibitor, is labelled for IM resistant and advanced Chronic Myeloid leukemia and could be an attractive alternative to IM especially in refractory and intolerant patients. We studied the clinical outcomes of 7 Pts who developed extensive ScGVHD at our institution. Among them, 5 had received prior IM. Patients' characteristics and transplantation modalities are summarised in table 1. Acute and cGVHD was scored according to standard criteria. All pts but one failed at least 3 lines of prior systemic immunosuppressive therapy. CGVHD features, responses to nilotinib and patients' outcomes are described in table 2. To our knowledge, this is the first report relating the impact of nilotinib on cGVHD setting. Although, tolerance to nilotinib has not been as good as we could expect, this drug appeared to be effective with manageable side-effects in some patients. One of the limitations of this study, is that nilotinib was used in patients with advanced cGVHD. Prospective studies are, therefore, warranted to investigate the efficacy and the tolerance of nilotinib in patients with less advanced disease. Table 1. Patients and transplantation characteristics Case N Age, y Sex, R/D diagnosis Conditioning/Stem cell source GVHD prophylaxis cGVHD sites Immunosuppression before nilotinib 1 30.5 M/F ALL MAC/BM CSA-MTX Mouth, skin eyes,liver CS-CSA-MMF-RTX-EVE 2 31 F/M AA MAC/PBSC CSA-CS-MMF Skin, mouth, eyes,bronchiolitis,joint contacture CS-TAC-MMF-EVE-IM 3 51.6 M/M HODG RIC/PBSC CSA-MTX Skin, mouth CS-CSA-MMF-IM 4 45.3 M/M AML MAC/BM CSA-MTX Skin, mouth, bronchiolitis, joint contracture CS-CSA-MMF-INO-ECP-RTX-AZA-IM 5 57.5 M/M MDS MAC/BM CSA-MTX Skin, bronchiolitis, joint contracture CS-CSA-MMF-RTX-ECP-IM 6 50.3 M/F CML MAC/BM CSA-MTX Skin, mouth, eyes, liver, joint contracture CS-CSA-MMF-ECP-IM 7 53.3 M/M AML MAC/BM CSA-MTX Skin none R/D: recipient/donor; aGVHD: acute graft versus host disease; cGVHD: chronic graft versus host disease; CML: chronic myeloid leukemia; MAC: myeloablative conditioning; BM: bone marrow; PBSC: peripheral blood stem cells; CSA: ciclosporine A; CS: corticosteroids, RIC: reduced intensity conditioning; MMF: mycophenolate mofetyl; AZA: azathioprine; MDS: myelodysplastic syndrome; MTX: metothrexate; RTX: rituximab; ECP: extracorporal photophere-sis; INO: inolimomab; HODG, hodgkin; AA: aplastic anemia; TAC: tacrolimus, ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia.; EVE: everolimus and IM: imatinib mesylate. Table 2. Outcome after nilotinib therapy Case N° Maximal tolerate dose of nilotinib, mg Nilotinb therapy duration at last follow up, mo Side effects/nilotinib discontinuation at last follow up cGVHD status at 2 mo of nilotinib cGVHD response in other organs at last follow up cGVHD status at last follow up Overall follow-up, mo Status at last follow up 1 800 3 None/yes failure – PR 69 alive 2 400 0.5 Pain swallowing, diarrhea/yes failure – progressive 46.8 Died of infection 3 800 2.5 Nausea, diarrhea/yes PR Mouth PR (>90%) 73.1 alive 4 800 7.5 None/yes MR Mouth progressive 72 alive 5 800 1 Cough, dyspnea, muscle cramps/yes PR bronchiolitis PR 59 alive 6 800 0.5 Headache, diarrhea/yes failure – PR 60.3 alive 7 800 7.5 None/no PR – PR 32 alive cGVHD indicates chronic graft versus host disease; PR, partial response and MR, minor response. Disclosures: No relevant conflicts of interest to declare.

This study investigated the impact of human herpesvirus type 6 (HHV6) reactivation within 100 days of allogeneic stem cell transplantation (allo-SCT) on patient outcomes. HHV6 plasma loads were monitored weekly by quantitative PCR. Of 235 consecutive patients, 112 (48%) had an early positive HHV6 PCR test (group A) and 123 (52%) did not (group B). HHV6 reactivation was less frequent in patients who received reduced-intensity conditioning (P = .028). In group A, only 6 patients (5%) were asymptomatic; the most common clinical manifestations were fever (n = 60), skin rash (n = 57), diarrhea (n = 51), pulmonary complications (n = 19), and neurologic disorders (n = 12). Compared with the patients in group B, those in group A experienced delayed platelet engraftment (P = .003) and more frequent grade II-IV acute graft-versus-host disease (GVHD) (47% versus 30% in group B; P = .009). In multivariate analysis, the most important factors influencing the development of grade II-IV acute GVHD development were early HHV6 reactivation (P = .03) and unrelated donor status (P < .001). HHV6 reactivation adversely influenced 6-month survival (P = .04). Of the 38 evaluable patients receiving antiviral treatment, 34 had a significantly decreased HHV6 load. Our findings indicate that HHV6 reactivation after allo-SCT is associated with delayed platelet engraftment, early posttransplantation mortality, and the development of acute GVHD. Careful monitoring of HHV6 by PCR is warranted during the early posttransplantation period.