Hidden in the Eyes-Recurrence of Systemic Hemopathies Reportedly "In Remission": Six Cases and Review of Literature.

Background and Objectives: Secondary ocular localizations of hematological malignancies are blinding conditions with a poor prognosis, and often result in a delay in the diagnosis. Materials and Methods: We describe a series of rare cases of ocular involvement in six patients with hematological malignancies, reportedly in remission, who presented secondary ocular localizations, challenging to diagnose. Two patients had an acute lymphoblastic leukemia (ALL) and developed either a posterior scleritis or a pseudo-panuveitis with ciliary process infiltration. One patient had iris plasmacytoma and developed an anterior uveitis as a secondary presentation. Two patients had a current systemic diffuse large B-cell lymphoma (DLBCL) and were referred either for intermediate uveitis or for papilledema and vitritis with secondary retinitis. Finally, one patient with an acute myeloid leukemia (AML) presented a conjunctival localization of a myeloid sarcoma. We herein summarize the current knowledge of ophthalmologic manifestations of extramedullary hematopathies. Results: Inflammatory signs were associated with symptomatic infiltrative lesions well displayed in either the iris, the retina, the choroid, or the cavernous sinus, from the admission of the patients in the ophthalmological department. These findings suggest that patients with ALL, AML, systemic DLBCL, and myeloma can present with ophthalmic involvement, even after having been reported as in remission following an effective systemic treatment and/or allograft. Conclusions: Early detection of hidden recurrence in the eyes may permit effective treatment. Furthermore, oncologists and ophthalmologists should be aware of those rare ocular malignant locations when monitoring patient's progression after initial treatment, and close ophthalmologic examinations should be recommended when detecting patient's ocular symptoms after treatment.

Core-binding factor acute myeloid leukemia in first relapse: a retrospective study from the French AML Intergroup.

Although core-binding factor-acute myeloid leukemia (CBF-AML) (t[8;21] or inv[16]/t[16;16]) represents a favorable cytogenetic AML subgroup, 30% to 40% of these patients relapse after standard intensive chemotherapy. The encouraging results of gemtuzumab ozogamicin (GO) in newly diagnosed AML, and particularly in CBF-AML, incited us to retrospectively investigate the impact of GO-based salvage in these patients. We retrospectively analyzed the outcome of 145 patients with CBF-AML (59 t[8;21], 86 inv[16]/t[16;16]) in first relapse. As salvage, 48 patients received GO-based chemotherapy and 97 patients received conventional chemotherapy. Median age was 43 years (range, 16-76). Median first complete remission duration was 12.1 months (range, 2.1-93.6). Overall, second complete remission (CR2) rate was 88%. With a median follow-up from relapse of 3.5 years, the estimated 5-year disease-free survival (DFS) was 50% and 5-year overall survival (OS) was 51%. Older age and shorter first complete remission duration was associated with a shorter OS. Patients treated with GO had similar CR2 rate but significantly higher 5-year DFS (68% vs 42%; P = .05) and OS (65% vs 44%; P = .02). In multivariate analysis, GO salvage was still associated with a significant benefit in DFS and OS. In the 78 patients who received allogeneic hematopoietic stem cell transplantation in CR2, GO before transplant significantly improved posttransplant DFS and OS without excess of treatment-related mortality.

Management of acute radiation syndrome.

Acute radiation syndrome encompasses a spectrum of pathological manifestations resulting from exposure to high doses of ionizing radiation. This syndrome typically progresses through three stages with a prodromal phase, a latency phase and a critical phase. Each of them varies in intensity and duration depending on the absorbed dose of radiation. Predominantly affecting the bone marrow, skin, and gastrointestinal tract, its clinical implications are profound and multiorgan failure must be considered. Radiation doses below 2 Gray generally result in insignificant clinical consequences, while exposures surpassing 12 Gray exceeds current therapeutic capacities. Survival outcomes for patients within this therapeutic range depend on their ability to withstand radiation-induced aplasia, compounded by an increased risk of bleeding and infection due to skin, gastrointestinal, and potentially combined radiation injuries. Assessing the degree of radiation exposure plays a pivotal role in tailoring patient management strategies and is based on a combination of clinical, biological, and physical parameters. Treatment approaches primarily include intensive hematologic support to manage symptomatic manifestations and etiologic treatment is now based on the administration of growth factors. The role of hematopoietic stem cell transplant (HSCT) will be carefully considered on an individual basis, especially for patients who do not respond following 3 weeks of cytokine therapy. This review highlights the pathophysiological mechanisms, assessment modalities, and therapeutic interventions crucial for managing acute radiation syndrome aiming to optimize patient outcomes and guide clinical practice.

Peripherally inserted central catheter placement in cancer patients with profound thrombocytopaenia: a prospective analysis.

OBJECTIVE: No studies have specifically evaluated the safety of peripherally inserted central catheter (PICC) placement in patients with profound thrombocytopaenia. We prospectively determined the frequency of haemorrhagic complications of PICC placement in cancer patients with uncorrected profound thrombocytopaenia. METHODS: Profound thrombocytopaenia was defined as a platelet count <50 × 10(9)/l. No patients received transfusions before or after the procedure. Three types of adverse effects were analysed: minor oozing, mild haematoma and major haemorrhage. RESULTS: One hundred and forty-three PICC implantations in 101 cancer patients were prospectively included in the study: seven patients (7 %) had a solid tumour and 94 (93 %) a haematological malignancy. Among these 143 procedures in thrombocytopaenic patients, 93 (65 %) were performed with a platelet count 20-50 × 10(9)/l and 50 (35 %) had lower than 20 × 10(9)/l. No major haemorrhage was observed. Minor oozing was observed in six implantations (4 %) and mild haematoma in two (1.5 %), for a total of eight minor haemorrhagic adverse events (5.5 %). In patients with a platelet count <20 × 10(9)/l, 1/50 (2 %) had minor oozing and none had minor haematoma. CONCLUSIONS: In cancer patients with uncorrected profound thrombocytopaenia, the incidence of adverse events after PICC implantation was low, and was limited to minor haemorrhagic adverse events. KEY POINTS: • PICC placement has high technical success in profound thrombocytopaenic cancer patients. • Few adverse events are encountered after PICC placement, limited to minor haemorrhage. • PICC placement does not routinely require platelet transfusion in patients with thrombocytopaenia. • Such PICC placement still seems safe when the platelet count is <20 × 10 (9) /l.

Effective use of intensive treatment against multiple myeloma of recipient origin after allogeneic transplantation for acute myeloid leukemia.

We describe here a 56-years -old woman cured in our institution for an acute myeloid leukemia (AML) and a monoclonal gammopathy of undetermined significance (MGUS). In order to treat AML, underwent allogeneic stem cell transplantation in second complete remission. Four years after transplant, MGUS evolved to multiple myeloma and was intensively treated with "autologous" transplant after successful mobilization. This report illustrates: (i) a lack of efficacy of graft versus myeloma effect in a patient probably cured of AML by graft versus leukaemia effect; (ii) the ability to mobilize peripheral blood stem cells in order to perform "autologous" transplantation after allogeneic transplantation.

Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning.

BACKGROUND: Due to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLA-matched sibling donor after this conditioning regimen. DESIGN AND METHODS: We analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day × 5 days). RESULTS: Median age was 21 years (range 4-43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II-IV graft-versus-host disease was 23% (95%CI 13-34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20-46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P = 0.017). With a median follow up of 73 months (range 8-233), the estimated 6-year overall survival was 87% (95% CI 78-97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin's lymphoma) during follow up. CONCLUSIONS: Cyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.

Hepatitis E and Allogeneic Hematopoietic Stem Cell Transplantation: A French Nationwide SFGM-TC Retrospective Study.

Usually self-limited, hepatitis E virus (HEV) infection may evolve to chronicity and cirrhosis in immunosuppressed patients. HEV infection has been described in solid-organ transplantation and hematology patients, but for allogeneic hematopoietic stem cell transplant (alloHSCT) recipients, only small cohorts are available. This retrospective nationwide multi-center series aimed to describe HEV diagnostic practices in alloHSCT French centers, and the course of infection in the context of alloHSCT. Twenty-nine out of 37 centers participated. HEV search in case of liver function tests (LFT) abnormalities was never performed in 24% of centers, occasionally in 55%, and systematically in 21%. Twenty-five cases of active HEV infection were diagnosed in seven centers, all because of LFT abnormalities, by blood nucleic acid testing. HEV infection was diagnosed in three patients before alloHSCT; HEV infection did not influence transplantation planning, and resolved spontaneously before or after alloHSCT. Twenty-two patients were diagnosed a median of 283 days after alloHSCT. Nine patients (41%) had spontaneous viral clearance, mostly after immunosuppressive treatment decrease. Thirteen patients (59%) received ribavirin, with sustained viral clearance in 11/12 evaluable patients. We observed three HEV recurrences but no HEV-related death or liver failure, nor evolution to cirrhosis.

Transcriptome analysis of bone marrow mesenchymal stromal cells from patients with primary myelofibrosis.

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm whose severity and treatment complexity are attributed to the presence of bone marrow (BM) fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironmental niches. Within these niches, mesenchymal stromal cells (BM-MSC) play a hematopoietic supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic stem/progenitor cells. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic stem/progenitor cell deregulation that features PMF.

Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis.

Primary myelofibrosis is a myeloproliferative neoplasm that is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize primary myelofibrosis, which is also associated with bone marrow stromal alterations marked by fibrosis, neoangiogenesis, and osteomyelosclerosis. In particular, contributions to primary myelofibrosis from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that bone marrow MSCs from primary myelofibrosis patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. Primary myelofibrosis-MSC overexpressed heparin-binding cytokines, including proinflammatory TGFß1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGFß1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in primary myelofibrosis-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibition of the endogenous TGFß1 receptor TGFßR1 impaired osteogenic differentiation in these MSCs. Taken together, our results define the source of a critical osteogenic function in primary myelofibrosis that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in primary myelofibrosis patients may heighten therapeutic efficacy.

[Acute myeloid leukemia with t(8;21): unusual cytological presentation and immunophenotype]. / Leucémie aiguë myéloïde à t(8;21) : présentation cytologique et immunophénotype inhabituels.

We report the case of a 20 years old woman with unusual acute myeloid leukemia t(8;21). Cytological, phenotypic and cytogenetic investigations showed a divergence from those of the literature as well as data for the last 12 LA to t(8;21) supported in the service.

[Association between multiple myeloma and acute myeloid leukemia secondary to myelodysplastic syndrome]. / Association d'un myélome multiple et d'une leucémie aiguë myéloïde secondaire à un syndrome myélodysplasique.

We report a rare case of association of two distinct hematologic malignancies: refractory cytopenia with multilineage dysplasia associated with del(5q) and symptomatic multiple myeloma associated with del(17p) and del(13q). After 16 months, the patient presented an acute leukemic transformation of the myelodysplasic syndrome.

[Signification of Epstein-Barr virus detection in the cerebrospinal fluid of a patient with human immunodeficiency virus related Burkitt lymphoma]. / Signification de la détection du virus d'Epstein-Barr dans le liquide céphalorachidien d'un patient suivi pour un lymphome de Burkitt lié au virus de l'immunodéficience humaine.

The significance of Epstein-Barr virus detection in the cerebrospinal fluid of patients with Burkitt lymphoma is poorly studied. We report the case of a patient with immunodeficiency associated Burkitt lymphoma in complete remission who presented 5 months after the end of treatment, an isolated optic neuritis. Lumbar puncture found lymphocytic meningitis and the viral load of Epstein-Barr virus was 234,000 copies per milliliter in the cerebrospinal fluid. These symptoms could be explained by Epstein-Barr virus meningoencephalitis but the detection of MYC rearrangements in the cerebrospinal fluid confirms the diagnosis of Burkitt lymphoma cerebral relapse. The detection of the Epstein-Barr virus DNA in the cerebrospinal fluid should be interpreted with caution.

[Light-chain escape from plateau phase]. / Échappement des chaînes légères de la phase de plateau.

We report the first case of light-chain escape from plateau phase occurring after 7 years of evolution of multiple myeloma in a patient who had never received new molecules. A very good partial response was obtained.

[Plasmacytoïd dendritic cells acute leukemia: a case report]. / Leucémie aiguë dérivée des cellules dendritiques plasmacytoïdes : à propos d'un cas.

We describe a case of a patient hospitalized in haematology unit for treatment to blastic plasmacytoid dendritic cell neoplasm. Apart skin lesions found at diagnosis in 83% of patients, few elements suggest the diagnosis. Cytology is not characteristic and no cytogenetic abnormality is specific to the LpDC, the karyotype shows generally at least three cytogenetic abnormalities. Definitive diagnosis rests to identification of a blastic population with immunophenotype CD4+ CD56+. This leukemia is chemosensitive but the relapse rate is important and the survival time is 16 months.