[Pyoderma gangrenosum following hematopoietic stem cell transplantation]. / Pyoderma gangrenosum après allogreffe de cellules souches hématopoïétiques.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare form of neutrophilic dermatosis and is a potential complication in a number of systemic diseases. These include blood diseases, which represent 3.5% of cases, with the main forms being monoclonal gammopathy and acute myeloid leukemia. PATIENTS AND METHODS: Herein we report a case of pyoderma gangrenosum in a female patient who had undergone haematopoietic stem cell allograft six months earlier as part of her treatment for acute T-cell leukemia. DISCUSSION: This condition forms one of the general disorders potentially associated with PG and is a dermatological disorder that can occur in marrow graft patients.

Complex upper arm reconstruction using an antero-lateral thigh free flap after an extravasation of Yttrium-90-ibritumomab Tiuxetan: A case report and literature review.

Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) is used in the treatment of non- Hodgkin's lymphoma. Extravasation is an iatrogenic complication that is fortunately rare. However, the treatment of this complication is often complex due to the risk of extensive skin necrosis and unpredictable evolution of localized irradiation. This vesicant drug requires emergency management when extravasation occured. Radiations burns have specificities. Therefore, wound coverage involves specific plastic surgical techniques. Here, we report the case of a man presenting a chronic and extensive skin necrosis of upper arm treated with an antero-lateral thigh free flap. Moreover, we compare our experience of Zevalin® extravasation management to other past publications and propose recommendations to prevent this unacceptable complication.

Fractionated doses of gemtuzumab ozogamicin combined with 3 + 7 induction chemotherapy as salvage treatment for young patients with acute myeloid leukemia in first relapse.

Current salvage therapies for relapsed acute myeloid leukemia (AML) are unsatisfactory. We retrospectively evaluated the efficacy and toxicity of fractionated doses of gemtuzumab ozogamicin (GO) combined with a standard 3 + 7 induction regimen in young patients with AML in first relapse. Salvage regimen consisted of GO 3 mg/m² on days 1, 4, and 7; cytarabine, 200 mg/m² on days 1-7; and daunorubicine, 60 mg/m²; or idarubicine, 12 mg/m² on days 1-3. Fourteen patients were treated between April 2008 and April 2011. Median age was 46 years (29-58), median white blood cell count is 3.4 109/L (0.9-19), and median first complete remission (CR) duration is 11 months (1-42). All the patients had previously received high or intermediate doses of cytarabine as consolidation therapy. Salvage treatment was performed as scheduled for the 14 patients, using daunorubicine in 12 patients and idarubicine in two. Overall response rate was 79 % with six CR and five CR with incomplete platelet recovery. Median times to neutrophil (>0.5 109/L) and platelet (>20 109/L) recovery were 29 days (23-32) and 36 days (28-48), respectively. Allogeneic transplantation was performed in the 11 responding patients within a median time of 4 months (3-10). Three mild and one moderate veno-occlusive disease (VOD) occurred after salvage and two moderate VOD after transplantation. Median and 2-year overall survival (OS) were 10 months and 42 %, respectively. For responders, estimated 2-year OS was 53 % (median OS not reached). This salvage regimen seems safe and effective in younger patients with AML in first relapse allowing allogeneic transplantation in CR2 for most patients.

Which role for rituximab in hairy cell leukemia? Reflections on six cases.

Hairy cell leukemia (HCL) is a rare, chronic, B-cell, lymphoproliferative disorder. Treatment has been revolutionized by the advent of interferon (IFN)-alpha and purine analogs (PA). First-line therapy with PA yields complete response rates of 75-100%, with many long-lasting remissions. In the event of profound neutropenia and/or infectious complications, a short sequence of IFN-alpha may precede PA treatment. Because of the excellent results achieved with PA therapy, the potential role of rituximab (an anti-CD20 monoclonal antibody that is highly effective against most B-cell lymphomas) in HCL has yet to be elucidated. Six HCL cases treated with rituximab are reported herein with a view to elucidating the potential role of the drug in HCL. The indications essentially consist of relapsing or refractory disease, avoiding the cumulative toxicity of PA, consolidation therapy in order to eradicate minimal residual disease, and first-line therapy for patients with contraindications to PA and IFN-alpha.

[Hematological disorders and hypereosinophilias]. / Hyperéosinophilies et affections hématologiques.

Hematological disorders are the third cause of hypereosinophilia, after allergic and parasitic diseases. Hematological disorders associated with hypereosinophilias can be classified as clonal, reactive or idiopathic, and recently the improvements of cytogenetic, molecular biology and immunology have allowed to revisit numerous cases previously diagnosed as idiopathic hypereosinophilic syndrome. Reactive eosinophilias are mainly associated with lymphoma or abnormal, often clonal T lymphoid population. Clonal eosinophilia is related either to various myeloid malignancies or to a genuine myeloproliferative disorder from the eosinophile lineage, the so-called chronic eosinophilic leukaemia. Chronic eosinophilic leukaemia can be associated with recurrent genes rearrangements involving PDGFRA, PDGFRB and FGFR1 or with clonal abnormalities not yet categorized. Idiopathic hypereosinophilic syndrome remains an exclusive diagnosis in presence of moderate or severe unexplained eosinophilia with target organ damage. The purpose of the diagnostic work-up of hypereosinophilic syndrome is to evidence either an abnormal T cell population or a clonal haematopoiesis. Imatinib mesylate dramatically improves chronic eosinophilic leukaemias associated with PDGFR abnormalities, while corticosteroids are still the main treatment for the other patients. In a near future, advances could arise from identification of new genes involved in clonal eosinophilia or in alternative therapy such as the anti-IL-5 antibodies.

[Autoimmune hemolytic anemia and immune thrombocytopenia associated with Hodgkin disease: Retrospective monocentric study]. / Cytopénies auto-immunes associées au lymphome de Hodgkin : étude rétrospective monocentrique.

INTRODUCTION: Hodgkin's lymphoma (HL) is less common than non-Hodgkin lymphoma and is rarely associated with autoimmune cytopenia. METHOD: We report a consecutive, monocentric and retrospective series of HL patients diagnosed with concomitant or subsequent autoimmune cytopenia over a period of 8 years. RESULTS: We report 4 out of 84 HL patients (4.8%) diagnosed with autoimmune cytopenia (4 immune thrombocytopenia including 2 Evans' syndromes). They were 4 males (average age 24 years for the 3 youngest, and one over 60 years old). Autoimmune cytopenia revealed lymphoma in 2 patients and occurred after HL treatment in the two other patients (5 and 36 months from the end of chemotherapy) without HL relapse. All cytopenias were resistant to conventional treatments (glucocorticoids, intravenous immune globulin, rituximab) and sensitive to chemotherapy when indicated for HL treatment. CONCLUSION: In our series, the predominance of males, a higher frequency of immune thrombocytopenia than autoimmune hemolytic anemia, the resistance to usual treatments and the efficacy of specific chemotherapy were consistent with the literature. Unexpectedly, patients were young and with nodular sclerosis morphology (vs. mixed cellularity) in 3 of 4 cases.

[ABO incompatibility and non myeloablative allogeneic stem cell transplantation]. / Incompatibilité ABO et greffe allogénique de cellules souches hématopoïétiques à l'ère des conditionnements non myéloablatifs.

ABO incompatibility is not a barrier for allogeneic hematopoietic stem cell transplantation but is associated with specific complications. Major ABO incompatibility is associated with delayed erythroid engraftment, increased transfusion requirement and cases of pure red cell aplasia. Minor ABO incompatibility may be responsible for acute haemolytic reactions in the first months following transplantation. The widely used non myeloablative conditioning regimens might modify the management of ABO incompatibility. They could favour pure red cell aplasia development in the setting of major ABO mismatch since they are associated with a prolonged persistence of host anti-donor isohemagglutinins after allogeneic hematopoietic stem cell transplantation. In the setting of minor ABO incompatibility, the use of peripheral blood stem cells and the nature of graft-versus-host disease prophylaxis regimen may have an impact on the incidence of haemolytic reactions. In that review, the clinical and therapeutic aspects of ABO incompatibility are studied, especially regarding the impact of the conditioning regimen intensity.

Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy.

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68-48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04-16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17-0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease.

[Hodgkin's disease with bone marrow involvement. The role of positron tomography]. / Maladie de Hodgkin avec atteinte médullaire. Intérêt de la tomodensitométrie par émissions de positons.

INTRODUCTION: Hodgkin's disease with initially predominant bone marrow involvement is observed in 1% of cases. OBSERVATION: A case of Hodgkin's disease with massive bone marrow invasion, manifested by pancytopenia in the context of fever and alteration in general status of health, with little or non superficial peripheral lymph nodes. The bone marrow biopsy revealed extensive myelofibrosis with rare Reed-Sternberg cells. DISCUSSION: This case report is inscribed within the framework of the exceptional massive bone marrow forms of Hodgkin's disease, described by Duhamel et al. in 1979. We believe that metabolic imaging with 18F-FDG positron emission tomography (PET) is a valid examination in orienting diagnosis and post-therapy assessment.

[A 7-year survey of strains identified in blood cultures in a clinical hematology unit]. / Etude sur sept ans des isolats d'hémocultures dans un service d'hématologie clinique.

GOAL: This study had for aim to analyze the epidemiology of strains identified in blood cultures (hôpital d'instruction des armées Percy, Clamart, France, hematology unit) to compare the rate of identified micro-organisms with literature data, and to search for a possible correlation between antibiotherapy management and evolution of resistance profiles. MATERIAL AND METHODS: All the micro-organisms (N = 690) collected over seven years (January 1996 to December 2002), from blood cultures of hospitalized patients in conventional and sterile sector were studied. RESULTS: Gram positive cocci rate (GPC) was 62.6% and Gram negative bacilli (GNB) 31.3%. Evolution in time showed a decrease of GPC and an increase of GNB, notably the non fermenting Gram negative bacilli, leading to an equal rate by 2001-2002. The most frequently identified species were Staphylococcus epidermidis (36.4%), Escherichia coli (8.7%), Pseudomonas aeruginosa (6.8%), and Staphylococcus aureus (4.9%). The rate of methicillin-resistant staphylococci was 63.6%. Fifty-five percent of E. coli strains had a penicillinase phenotype. Pseudomonas aeruginosa resistance was 8.5, 8.5, 6.4 and 8.5%, respectively for ceftazidime, piperacillin-tazobactam, imipenem, and amikacin. CONCLUSION: This study showed a tendency to inversion of former bacteremia epidemiology with increasing negative Gram bacilli. It justifies the antibiotherapy protocols adopted in the hematology unit.

An 8-year survey of strains identified in blood cultures in a clinical haematology unit.

The aim of our study was to determine the epidemiological profile and the antibiotic susceptibility of bacteria and fungi identified from blood cultures in the patients of the clinical haematology unit. A retrospective study was carried out over an 8-year period (2003-2010) in the clinical haematology unit of the Percy Military Medical Center. During this period, we collected 723 isolates: Gram-negative bacilli (70.8%) and Gram-positive cocci (18.7%). The four most commonly isolated species were Escherichia coli (18.5%), Pseudomonas aeruginosa (14.8%), Stenotrophomonas maltophilia (6.2%) and Staphylococcus epidermidis (5.4%). The rate of methicillin-resistant Staphylococcus aureus was 6.45% and that of coagulase-negative staphylococci 61.2%. No resistance to glycopeptides was observed. In E. coli, as in the Klebsiella-Enterobacter-Serratia group, a 27% resistance to fluoroquinolones was observed. Concerning P. aeruginosa, the phenotypes were distributed over penicillinase (23.4%) and cephalosporinase (13.1% were resistant to ceftazidime). The impermeability rate of imipenem was 9.3%. The aggressiveness and duration of haematological treatments explains why infections remain one of the main complications of neutropenia. The emergence of new or unusual bacteria is highly likely. Antibiotic selective pressure and long periods of hospitalization could explain the emergence of multiresistant bacteria. As a consequence, epidemiological surveillance is indispensable.

SP/drug efflux functionality of hematopoietic progenitors is controlled by mesenchymal niche through VLA-4/CD44 axis.

Hematopoiesis is orchestrated by interactions between hematopoietic stem/progenitor cells (HSPCs) and stromal cells within bone marrow (BM) niches. Side population (SP) functionality is a major characteristic of HSPCs related to quiescence and resistance to drugs and environmental stresses. At steady state, SP cells are mainly present in the BM and are mostly absent from the circulation except in stress conditions, raising the hypothesis of the versatility of the SP functionality. However, the mechanism of SP phenotype regulation is unclear. Here we show for the first time that the SP functionality can be induced in lin(-) cells from unmobilized peripheral blood after nesting on mesenchymal stromal cells (MSCs). This MSC-induced SP fraction contains HSPCs as demonstrated by their (i) CD34(+) cell percentage, (ii) quiescent status, (iii) in vitro proliferative and clonogenic potential, (iv) engraftment in NSG (NOD SCID gamma chain) mice and (v) stemness gene expression profile. We demonstrate that SP phenotype acquisition/reactivation by circulating lin(-) cells is dependent on interactions with MSCs through VLA-4/α4ß1-integrin and CD44. A similar integrin-dependent mechanism of SP phenotype acquisition in acute myeloid leukemia circulating blasts suggests an extrinsic regulation of ATP-binding cassette-transporter activity that could be of importance for a better understanding of adhesion-mediated chemoresistance mechanisms.

[Evans syndrome: be careful of over-diagnosis]. / Syndrome d'Evans: attention aux diagnostics par excès.

INTRODUCTION: Evans syndrome (ES) is characterized by the coexistence of an autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Despite being frequently evocated in the simultaneous presence of anemia and thrombocytopenia, this rare disease only accounts for 0.8 to 3.7% of patients with ITP or AIHA. CASE REPORTS: We report three suspected cases of ES, diagnosed in the presence of thrombocytopenia and hemolytic anemia association, with a positive direct Coombs test in two patients. Standard ES treatment failure and occurrence of additional features subsequently led to correct diagnosis to thrombotic thrombocytopenic purpura, myelodysplastic syndrome with AIHA, and ITP with hemorrhagic anemia, respectively. CONCLUSION: Bicytopenias, even in an immunological context, are not sufficient to ascertain ES diagnosis. Our cases illustrate the diagnostic difficulties that may arise in daily practice, and induce over-diagnosis of this rare disease.

Does addition of erythropoiesis stimulating agents improve the outcome of higher-risk myelodysplastic syndromes treated with azacitidine?

We studied a retrospective cohort of 282 higher-risk MDS treated with azacitidine, including 32 patients who concomitantly received an ESA for a median of 5.8 months after azacitidine onset. Forty-four percent of ESA and 29% of no-ESA patients reached HI-E (p=0.07); 48% and 20% achieved transfusion independence (p=0.01). Median OS was 19.6 months in the ESA and 11.9 months in the no-ESA groups (p=0.04). Addition of an ESA significantly improved OS (p=0.03) independently of azacitidine schedule and duration, and of our proposed azacitidine risk score (Blood 2011;117:403-11). Adding an ESA to azacitidine in higher-risk MDS should be studied prospectively.

[Acute respiratory distress revealing acute myeloblastic leukaemia: case report]. / Détresse respiratoire aiguë révélant une leucémie aiguë myéloblastique. À propos d'un cas.

We report on the case of a patient diagnosed with acute leukaemic transformation of chronic myelomonocytic leukaemia. Its development was characterised by blastic pulmonary localisation and response to corticosteroids. We discuss the etiologies of respiratory distress in acute myeloblastic leukaemia and the corticosteroid sensitivity of this myeloid disease.

Impact of nonmyeloablative conditioning regimens on the occurrence of pure red cell aplasia after ABO-incompatible allogeneic haematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: In the setting of major ABO-incompatible allogeneic haematopoietic stem cell transplantation (HSCT), pure red cell aplasia (PRCA) is linked to the persistence of host residual plasma cells secreting antidonor isohaemagglutinins (HA) after transplantation. There are conflicting results regarding the impact of the intensity of conditioning regimen on the occurrence of PRCA after major ABO-mismatched HSCT. MATERIAL AND METHODS: To address this question, we compared two cases occurring after nonmyeloablative (NMA) and myeloablative (MA) HSCT and reviewed previous cases reported in the NMA setting. RESULTS AND CONCLUSIONS: We observed a delayed disappearance of antidonor HAs in the NMA setting, associated to a more prolonged period of red blood cells transfusion dependence than in the MA setting. In our case as in several others, the disappearance of antidonor HAs and resolution of PRCA were observed after reinforcement of the graft-versus-host effect (i.e. immunosuppression removal or donor leukocytes infusion).