Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, these transplants are complicated by a high rate of relapse in very high cytogenetic risk or refractory diseases. The benefit of this therapeutic strategy for these serious malignant hemopathies could therefore be reassessed. As part of the 14th workshop for the harmonization of allograft practices organized by the francophone society of bone marrow transplantation and cellular therapy (SFGM-TC) (SFGM-TC) in Lille in September 2023, the role of allograft for very high risk or refractory AML and MDS was challenged after analysis of published studies.

BACKGROUND: Periarteritis nodosa (PAN) is a vasculitis affecting medium-vessel and may be associated with myelodysplastic syndrome. This association needs a simultaneous treatment of the vascular and the hematological disease. However limited data are available on the benefit of hematological treatment, and in particular allogeneic stem cell transplantation, in this situation.
METHODS: A 32-year-old patient with refractory periarteritis nodosa and simultaneous myelodysplastic syndrome, was treated with chemotherapy followed by hematopoietic stem cell allograft. The symptoms relating to PAN improved, allowing to decrease the dose of prednisone down to 5mg/d. However, a hematological relapse occurred two months later leading to the patient\'s death.
CONCLUSIONS: Hematopoietic stem cell allograft may represent a therapeutic option in the management of severe or refractory autoimmune diseases when the hematological indication is retained.

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.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the treatment options for myelodysplastic syndromes (MDS). This treatment is indicated as first-line treatment for high-risk MDS according to the IPSS and R-IPSS classifications and improves overall survival and progression-free survival. However, allo-HSCT is not indicated in first intention for low-risk MDS. It can be discussed in case of cytopenias needing transfusions, poor evolution under other treatment, or in case of poor prognosis molecular anomaly. Allo-HSCT is a treatment that can be complicated by early or late toxicities (graft versus host disease, infections, chemotherapy toxicity…). The decision to do an allo-HSCT is based on the benefit/risk ratio between the risk of progression from MDS to myeloid leukemia and the risk of transplant related mortality, which increases with the patient\'s age and comorbidities. The indication of a cytoreductive treatment before allo-HSCT depends on the blasts count, and on the delay before the allograft. The use of reduced intensity conditioning regimen and alternative donors such as haploidentical donors, expanded the indications for allo-HSCT. Relapse remains one of the main causes of mortality after allo-HSCT. Some genetic mutations and karyotype anomalies increase the risk of post-transplant relapse. Preventive treatments for relapse are currently being studied. Treatments such as azacytidine, donor lymphocytes infusions or targeted therapies can be used, prophylactically or preemptively.

Chemotherapy and radiotherapy for a previous cancer can lead to subsequent myelodysplastic syndrome (MDS). However, these therapy-related cases are hypothesized to explain only 5 % of diagnosed MDS cases. Environmental or occupational exposure to chemicals or radiations has also been reported to be associated with higher risk of MDS. The present review analyses those studies evaluating the association of MDS with environmental or occupational risk factors. There is sufficient evidence that environmental or occupational exposure to ionizing radiation or benzene can cause MDS. Tobacco smoking is also a sufficiently documented riskfactor for MDS. A positive association has been reported between exposure to pesticides and MDS. However, there is only limited evidence that this association could be causal.

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.

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BACKGROUND: Myelodysplasia (MDS) can occur as systemic manifestations such as connective tissue diseases or vasculitis. Rheumatological manifestations are also described in such context. Herein, we report the observation of a patient with chronic myelomonocytic leukemia (CMML) who developed systemic manifestations: polymyalgia rheumatica and pericarditis.
METHODS: A 78-year-old patient was referred for the exploration of two months history of inflammatory shoulder pain associated with biological inflammatory syndrome. He presented with asthenia, anorexia and loss of 5kg in one month. He had a three years follow-up for a CMML without any specific treatment. All of the explorations carried out showed a typical polymyalgia rheumatica. A pericardial effusion requiring emergency drainage was synchronously diagnosed. All the symptoms occurred during a worsening of his hematological disease. The rheumatological manifestation was favorable after a short corticosteroid therapy and pericarditis did not recur after 2 years of follow-up.
CONCLUSIONS: It should be necessary to screen patients for MDS in a context of systemic manifestation, especially in elderly patients with an abnormal blood count (cytopenia, macrocytosis and monocytosis).

BACKGROUND: Sweet\'s syndrome is an acute neutrophilic dermatosis characterized by abrupt onset of skin lesions accompanied by fever, arthralgia, leukocytosis and diffuse neutrophilic infiltration of the dermis, as well as an excellent response to corticosteroid therapy.
METHODS: A 46-year-old patient with myelodysplastic syndrome was admitted for chemotherapy. On the eighth day of chemotherapy, he received a single dose of pegfilgrastim. Three days later, he developed pyrexia, conjunctivitis, arthralgia and erythematous and painful papulo-nodular lesions. Broad-spectrum empiric antibiotic therapy was started but the patient\'s condition deteriorated. Biology showed pancytopenia and inflammatory syndrome. Microbiological tests, autoimmune serologies and chest-computed tomography were negative. Cutaneous biopsy was compatible with Sweet\'s syndrome. A diagnosis of Sweet\'s syndrome induced by pegfilgrastim was made and intravenous corticosteroid therapy was started with a rapid favorable outcome.
CONCLUSIONS: Sweet\'s syndrome is a rare adverse effect of G-CSF.

BACKGROUND: The vasculitis can be the consequence of malignancy: most often hematologic rather than solid tumors. The association between large vessels vasculitis and myelodysplastic syndrome is rare.
METHODS: A 55-year-old man experienced asthenia, fever, polyarthritis and inflammatory syndrome. Haematological investigations found a type 2 refractory anemia with excess blasts (RAEB-2) with discovery of severe anemia (Hb: 7,8g/dl) and thrombopenia (platelets: 40,000/mm3). Radiological examinations found thoracic aortitis and carotid vasculitis. Treatment in the form of steroids and azacitidine was instituted. The lack of control of both RAEB-2 and vasculitis was responsible for the death of the patient.
CONCLUSIONS: Myelodysplastic syndrome and large vessels vasculitis is a rare but serious association disease. The lack of efficiency of corticosteroids seems to be common. Prognosis depends on the haematological treatment effectiveness.