[Preventive and therapeutic strategies for relapse after hematopoietic stem cell transplant for pediatric AML (SFGM-TC)]. / Stratégies préventives et thérapeutiques de la rechute après allogreffe de cellules souches hématopoïétiques pour les LAM pédiatriques (SFGM-TC).

Treatment of pediatric high-risk acute myeloid leukemia (AML), defined either on molecular or cytogenetic features, relies on bone marrow transplant after cytologic remission. However, relapse remains the first post-transplant cause of mortality. In this 13th session of practice harmonization of the francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), our group worked on recommendations regarding the management of post-transplant relapse in AML pediatric patients based on international literature, national survey and expert opinion. Overall, immunomodulation strategy relying on both measurable residual disease (MRD) and chimerism evaluation should be used for high-risk AML. In very high-risk (VHR) AML with a 5-year overall survival ≤30 %, a post-transplant maintenance should be proposed using either hypomethylating agents, combined with DLI whenever possible, or FLT3 tyrosine kinase inhibitors if this target is present on leukemia cells. In the pre-emptive or early relapse settings (< 6 months post-transplant), treatments combining DLI, Azacytidine and Venetoclax should be considered. Access to phase I/II trails for targeted therapies (menin, IDH or JAK inhibitors) should be discussed in each patient according to the underlying molecular abnormalities of the disease.

[SFCE harmonization workshops: Neonatal acute myeloid leukemia]. / Orientation et prise en charge de la leucémie aiguë myéloïde néonatale : recommandations du comité leucémies de la SFCE.

Neonatal acute myeloid leukemias (AML) occurred within the first 28 days of life and constitute only a small proportion of all AL. They are distinguished from leukemias of older children by their clinical presentation, which frequently includes cutaneous localizations ("blueberry muffin rash syndrome") and a leukocytosis above 50 ×109/L. This proliferation may be transient, causing a transient leukemoid reaction in a background of constitutional trisomy 21 ("Transient Abnormal Myelopoieseis" or TAM) or Infantile Myeloproliferative Disease in the absence of constitutional trisomy 21 ("Infantile Myeloproliferative Disease" or IMD). In cases of true neonatal AML, the prognosis of patients is poor. Overall survival is around 35 % in the largest historical series. This poor prognosis is mainly due to the period of onset of this pathology making the use of chemotherapy more limited and involving many considerations, both ethical and therapeutic. The objective of this work is to review this rare pathology by addressing the clinical, biological, therapeutic and ethical particularities of patients with true neonatal AML or transient leukemoid reactions occurring in a constitutional trisomy 21 (true TAM) or somatic background (IMD).

[Suspicion of constitutional abnormality at diagnosis of childhood leukemia: Update of the leukemia committee of the French Society of Childhood Cancers]. / Suspicion d'anomalie constitutionnelle au diagnostic de leucémie chez l'enfant : mise au point du comité leucémies de la Société française des cancers de l'enfant.

The spectrum of childhood leukemia predisposition syndromes has grown significantly over last decades. These predisposition syndromes mainly involve CEBPA, ETV6, GATA2, IKZF1, PAX5, RUNX1, SAMD9/SAMD9L, TP53, RAS-MAPK pathway, DNA mismatch repair system genes, genes associated with Fanconi anemia, and trisomy 21. The clinico-biological features leading to the suspicion of a leukemia predisposition are highly heterogeneous and require varied exploration strategies. The study of the initial characteristics of childhood leukemias includes high-throughput sequencing techniques, which have increased the frequency of situations where a leukemia predisposing syndrome is suspected. Identification of a leukemia predisposition syndrome can have a major impact on the choice of chemotherapy, the indication for hematopoietic stem cell transplantation, and screening for associated malformations and pathologies. The diagnosis of a predisposition syndrome can also lead to the exploration of family members and genetic counseling. Diagnosis and management should be based on dedicated and multidisciplinary care networks.

[Optimizing the use of bosutinib in patients with chronic-phase chronic myeloid leukemia: Recommendations of a panel of experts from the Fi-LMC (French CML working group)]. / Optimisation du bosutinib dans la leucémie myéloïde chronique : recommandations du Fi-LMC (France Intergroupe des leucémies myéloïdes chroniques).

The treatment of chronic myeloid leukemia relies on orally available tyrosine kinase inhibitors targeting the BCR::ABL1 oncoprotein. Bosutinib is a second generation adenosine triphosphate-competitive inhibitor approved for use in frontline adult chronic phase-chronic myeloid leukemia and all phases-chronic myeloid leukemia in the second line setting or beyond. Its efficacy was demonstrated in several pivotal clinical trials at 400mg once daily in the first line context and at 500mg once daily beyond first line. Bosutinib-related adverse events frequently occur early after treatment initiation and include gastro-intestinal symptoms and cytolytic hepatitis. These drug-related adverse events must be properly managed in order to preserve safety, efficacy and treatment acceptability. The French chronic myeloid leukemia study group gathered a panel of experts in hematology, pharmacology and hepatology in order to elaborate practical recommendations on the management of bosutinib treatment. These recommendations aim at optimizing the short and long-term tolerance and benefit/risk balance of bosutinib, mainly focusing at gastro-intestinal and liver toxicities.

[CAR-T cells, an innovative therapy]. / Les CAR-Tcells, une thérapie innovante.

CAR-T cell therapy for patients with hematological malignancies has been practiced at the Basse-Normandie Hematology Institute since November 2022. This treatment requires the care pathway to be coordinated by the nurse coordinator. Nurses play a key role in the early diagnosis of side effects induced by this drug. Interdisciplinary collaboration and the value of teamwork are also emphasized.

Large granular lymphocyte lymphoma with leukemic phase and suspicion of leptomeningeal lymphomatosis in a cat - a case report.

INTRODUCTION: In this case report we present a feline large granular lymphocyte (LGL) lymphoma, a rare morphologically distinct subtype of lymphoma, in a twelve-year-old female spayed domestic short hair cat, with high suspicion of leptomeningeal lymphomatosis due to magnetic resonance imaging findings and results of cerebral spinal fluid analyses. Diagnosis of LGL lymphoma was confirmed by means of blood cytology and polymerase chain reaction for antigen receptor rearrangements.

INTRODUCTION: Dans ce rapport de cas, nous présentons un Large Granular Lymphocyte (LGL) lymphome, un sous-type rare de lymphome, chez une chatte domestique à poil court stérilisée de douze ans, avec une forte suspicion de lymphomatose leptoméningée en raison des résultats de l'imagerie par résonance magnétique et de l'analyse du liquide céphalo-rachidien. Le diagnostic de LGL-lymphome a été confirmé par une cytologie sanguine et une réaction en chaîne de la polymérase pour les réarrangements des récepteurs d'antigènes.

[Dysimmune manifestations associated with myelodysplastic neoplasms and chronic myelomonocytic leukaemias]. / Manifestations dysimmunitaires associées aux syndromes myélodysplasiques et leucémies myélomonocytaires chroniques.

Systemic inflammatory or autoimmune diseases (SIAD) are observed in up to a quarter of patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), with a broad clinical spectrum including asymptomatic biological abnormalities, isolated inflammatory clinical manifestations (recurrent fever, arthralgia, neutrophilic dermatoses…) or identified systemic diseases (giant cell arteritis, recurrent polychondritis…). Recent advances in molecular biology have shed new light on the pathophysiological mechanisms that link inflammatory manifestations and myeloid hemopathies, particularly in VEXAS syndrome following the identification of somatic mutations in the UBA1 gene, or in neutrophilic dermatoses with the concept of myelodysplasia cutis. Although the presence of SIAD does not seem to affect overall survival or the risk of transformation into acute myeloid leukemia, their treatment remains a challenge given the frequent high level of corticosteroid dependence as well as the poor efficacy and tolerance (cytopenias, infections) of conventional immunosuppressive agents. Recent prospective data supports the interest of a therapeutic strategy using demethylating agents and notably azacitidine to target the pathological clone.

[The place of IPA in the follow-up of elderly patients with acute myeloid leukemia]. / La place de l'IPA dans le suivi du patient âgé porteur d'une leucémie aiguë myéloïde.

Since 2020, a promising new treatment has been offered to elderly patients with acute myeloid leukemia. However, adverse events complicate their treatment, which is performed on an outpatient basis. The advanced practice nurse could provide assistance in the follow-up of these elderly and polypathological patients, who require regular clinical and biological monitoring, adaptation of their therapies and the establishment of city-hospital coordination likely to guarantee their maintenance at home.

Large granular lymphocyte leukemia: An indolent clonal proliferative disease associated with an array of various immunologic disorders.

Large granular lymphocyte leukemia (LGLL) is a chronic lymphoproliferative disorder characterized by the proliferation of T or NK cytotoxic cells in the peripheral blood, the spleen and the bone marrow. Neutropenia leading to recurrent infections represents the main manifestation of LGLL. One specificity of LGLL is its frequent association with auto-immune disorders, among them first and foremost rheumatoid arthritis, and other hematologic diseases, including pure red cell aplasia and bone marrow failure. The large spectrum of manifestations and the classical indolent course contribute to the diagnosis difficulties and the frequency of underdiagnosed cases. Of importance, the dysimmune manifestations disappear with the treatment of LGLL as the blood cell counts normalize, giving a strong argument for a pathological link between the two entities. The therapeutic challenge results from the high rate of relapses following the first line of immunosuppressive drugs. New targeted agents, some of which are currently approved in autoimmune diseases, appear to be relevant therapeutic strategies to treat LGLL, by targeting key activated pathways involved in the pathogenesis of the disease, including JAK-STAT signaling.

[Management of AML in the elderly]. / Prise en charge des LAM chez les sujets âgés.

Elderly patients with acute myeloid leukemia, ineligible for intensive chemotherapy, have long had a very poor prognosis and have always represented one of the main patient populations included in early phase clinical research trials. In recent years, many molecules have shown very interesting efficacy, often targeted therapies whose indication is based on a specific mutation profile (gilteritinib, ivosidenib), or mutation-independent (venetoclax), but also drugs whose indication is based on a specific biomarker (tamibarotene) or on new generation immunotherapies targeting macrophages (magrolimab) or other immune effectors while targeting leukemic cells resulting in forced immunological synapse (flotetuzumab) or activation of lymphocyte effectors associated with inhibition of the AML cells' stem signature in their microenvironment (cusatuzumab sabatolimab). All of these new strategies are discussed in this review, as well as the challenges of this frail population, which has benefited in recent months from all the major advances in the field, questioning in a second phase the modification of practices in younger patients.

[A particular presentation of a T cell large granular lymphocytic leukaemia]. / Une présentation particulière de leucémie à grands lymphocytes granuleux.

T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive neoplasm derived from post-thymic T cells. Patients are typically middle-aged with a slight male predominance who present with a high white blood cell count, hepatosplenomegaly, lymphadenopathy, and other symptoms typically associated with leukemia. Although cutaneous involvement has been reported in up to 30% of cases of T-PLL, to our knowledge, none have presented with a presentation resembling livedoid vasculopathy. In the correct clinical context, an underlying hematolymphoid neoplasm should be included in the differential diagnosis of a patient presenting with livedoid vasculopathy.

[Role of allogeneic hematopoietic cell transplantation after anti-CD19 CAR T-cell treatment: Guidelines from the SFGM-TC]. / Place de l'allogreffe de cellules souches hématopoïétiques après traitement par CAR T-cell anti-CD19 : recommandations de la SFGM-TC.

The role of allogeneic hematopoietic cell transplantation (allo-HCT) after CAR T- treatment cells in hematologic malignancies is currently controversial. Prolonged remissions after several years of follow-up suggest that there is a curative effect of CAR T-cells therapy, whereas allo-HCT was previously considered the only curative treatment in relapse situation. The aim of this harmonization workshop is to detail the existing data in the literature on the feasibility of allo-HCT after CAR T-cells and to propose to consider allograft in selected patients with B-acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). In B-ALL, various intrinsic factors (inherent to the patient, to the disease, to the type of CAR T-cells) and especially various post CAR T-cells criteria (early expansion kinetics, residual disease at D28, early loss of B-cell aplasia) should lead to consider performing allo-HCT before the occurrence of a relapse. In DLBCL, although there are risk factors for relapse at diagnosis and prior to CAR T-cells therapy, response assessed by PET-CT at three months is critical and allo-HCT cannot currently be recommended in cases of complete or partial remission. In any case, if the age is appropriate for allogeneic transplantation, HLA typing should be performed before CAR T-cells treatment in order not to delay the allo-HCT project if needed.

[Acute lymphoblastic leukemia in developing countries: Management from the transplant indication (allo/auto) until post-transplant follow-up. Guidelines from the SFGM-TC]. / Leucémie aiguë lymphoblastique dans les pays en voie de développement : prise en charge dès l'indication de greffe jusqu'au suivi post-greffe. Recommandations de la SFGM-TC.

Management of acute lymphoblastic leukemia (ALL) patients in countries with limited resources depends on the means of prognostic stratification, available treatment and logistics. During the 12th annual harmonization workshops of the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC), a designated working group reviewed the literature in order to elaborate unified guidelines for allogeneic hematopoietic cell transplantation (Allo-HCT) in this disease. Conventional poor prognostic factors can be used to determine the indication of allo-HCT in first remission. Patients lacking a HLA-matched related donor can be allografted with a haploidentical donor allo-HCT if available. Chemotherapy based conditioning regimen can be used if TBI is not available, because the probability to find a radiotherapy department with the capacity for total body irradiation is low. For patients with Philadelphia chromosome positive (Phi+) ALL, post-transplantation tyrosine kinase inhibitors as a systematic maintenance strategy is recommended. Autologous HCT is optional for Phi+ ALL patients with negative minimal residual disease, who not eligible for allo-HCT. Patients with refractory/relapsed disease have a poor prognosis which highlights the importance of acquiring in the future new therapies such as: blinatumumab, inotuzumab, and CAR-T cells.

[Invasive fungal infections in immunocompromised children in paediatric haematology: Recommendations for management in SFCE centres]. / Infections fongiques invasives chez l'enfant immunodéprimé en hématologie pédiatrique : recommandations de prise en charge au sein des centres de la SFCE.

INTRODUCTION: To date, invasive fungal infections (IFIs) are still responsible for a high mortality rate in children managed for haematological malignancy. Although Candida and Aspergillus infections remain in the majority, emerging fungal infections are increasingly common. Children differ from adults in their pathology and treatment, as well as in their prior fungal colonisation and unique pharmacokinetics. Therefore, we propose here specific paediatric management recommendations for IFIs in haematology. METHODS: We based our recommendations on a review of the literature, including the latest ECIL recommendations, an analysis of practices and a collection of expert opinions. RESULTS AND DISCUSSION: In France, approximately 5% of children treated for haematological malignancy or who have received a bone marrow allograft present an IFI. These IFIs are equally divided between yeast infections (mainly due to Candida albicans) and filamentous infections (mainly aspergillosis) and 16% are IFIs due to emerging fungi, half of which are due to Mucorales. In these recommendations, we recall the diagnostic criteria for proven or probable IFI according to the Donnelly classification, then we propose strategies for screening, diagnosing, evaluating the extension and treating these three types of IFI. We also detail the diagnostic and therapeutic management of chronic disseminated candidiasis. We also discuss prophylactic measures, including environmental measures which are of primary importance in children.

[Prevention and management of pegaspargase associated-toxicities (excluding coagulation abnormalities). Recommendations of the French Society of Children and Adolescent Cancers (Leukemia committee)]. / Prise en charge des toxicités de la pégaspargase (hors anomalies de la coagulation). Recommandations du comité leucémie de la Société française de lutte contre les cancers de l'enfant et de l'adolescent.

Pegaspargase (Oncaspar®), a pegylated form of native Escherichia Coli-derived L-asparaginase is an essential component chemotherapy used in the treatment of acute lymphoblastic leukemia (ALL) in pediatric and adult patients. Its particular toxicity profile requires a specific management to improve safety and tolerability and optimize treatment outcome and therefore survival. Within the framework of workshops of practice harmonization of the French Society of Children and Adolescent Cancers, diagnostic and management of the most commonly occuring toxicities (excluding coagulation abnormalities) during Pegaspargase treatment were reviewed according to the analysis of published studies.