Hematopoietic stem cell transplantation in the Eastern Mediterranean Region (EMRO) 2011-2012: A comprehensive report on behalf of the Eastern Mediterranean Blood and Marrow Transplantation group (EMBMT).

OBJECTIVE/BACKGROUND: The Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) group has accumulated over 31 years of data and experience in hematopoietic stem cell transplantation (HSCT), particularly in hemoglobinopathies, severe aplastic anemia, inherited metabolic and immune disorders, in addition to a wide array of hematologic malignancies unique to this region. A regional update in current HSCT trends is highly warranted. We studied the trends of HSCT activities in World Health Organization-Eastern Mediterranean (EMRO) region, surveyed by the EMBMT, between 2011 and 2012. METHODS: Retrospective analysis of the survey data mainly of cumulative number of transplants, types of transplants (autologous vs. allogeneic), types of conditioning such as myeloablative versus reduced intensity was conducted. Also, trends in leukemias, hemoglobinopathies, severe aplastic anemia, inherited bone marrow failure syndromes, amongst others were analyzed. RESULTS: Twenty-one teams from nine EMRO countries reported their data (100% return rate) to the EMBMT for the years 2011-2012, with a total of 3,546 first HSCT (1,670 in 2011; 1,876 in 2012). Allogeneic HSCT (allo-HSCT) represented the majority (62%) in both years. The main indications for allo-HSCT were acute leukemias (988; 46%), bone marrow failure syndromes (421, 20%), hemoglobinopathies (242; 11%), and immune deficiencies (157; 7%). There was a progressive increase in the proportions of chronic myeloid leukemia cases transplanted beyond first chronic phase (37 [7%] of all chronic myeloid leukemia cases in 2011 vs. 39 [29%] in 2012). The main indications for autologous transplants were multiple myeloma/plasma cell disorders (510; 39%), Hodgkin lymphoma (311; 24%), non-Hodgkin lymphoma (259; 20%), and solid tumors (163; 12%). Reduced intensity conditioning continued to show a progressive decrease over years (9.5% in 2011 vs. 7.9% in 2012), yet remained relatively low compared with contemporary practices in Europe published by EBMT. The vast majority (91%) of allo-HSCT source was from sibling donors with continued dominance of peripheral blood (64%) followed by bone marrow (33%).While umbilical cord blood transplants increased to 4% of allo-HSCT, matched unrelated donor remained underutilized and there was no haplo-identical transplant reported. Large centers with >50 HSCT/year, showed a continued increase in the total number of allo-HSCT over the past 2years that may be related to capacity building issues and require further studies. CONCLUSION: There is a discernable increase of HSCT rate in the EMRO region with a significant expansion in utilization of cord blood transplants and allogeneic peripheral blood-HSCT as a valuable source. However, further research of outcome data and the development of regional donor banks (cord blood and matched unrelated donors) may help to facilitate future planning to satisfy the escalating regional needs and augment collaboration within the EMBMT and globally.

Association of glutathione S-transferase (GSTM1 and GSTT1) genes with chronic myeloid leukemia.

Chronic myeloid leukemia (CML), as most of cancers results from a complex interaction between genetic or non genetic factors. Exposures to xenobiotics endogenous or exogenous associated with a reduced individual ability in detoxifying activity, constitutes a risk of developing cancer. It is known that polymorphism of glutathione S-transferases (GSTs) genes affects the detoxification of xenobiotics. Thus, we conducted a case-control study in which 92 patients (Mean age ± SD, 40.62 ± 12.7 years) with CML and 93 healthy unrelated controls (Mean age ± SD, 41.38 ± 13.4 years) have participated. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction. Logistic regression was used to assess the possible link between GSTM1 and GSTT1 null genotypes and CML as well as between combined genotypes and CML. GSTM1 null genotype frequency was slightly higher in patients than control (48.9% vs. 40.9%) but, it was not associated with CML (OR 95% CI, 1.4, 0.78-2.48; p = 0.271). Moreover, GSTT1 null genotype frequency showed a similar trend between patients and control (17.4% vs. 9.7%; OR 95% CI, 1.97, 0.82-4.71; p = 0.13). Surprisingly, GSTT1 null genotype was significantly associated with the risk of CML in males (OR 95% CI, 5, 1.25-20.1; p = 0.023). The combined GSTM1 present/GSTT1 null genotype was found to have a limited effect against the risk of CML (OR 95% CI, 0.3, 0.08-0.99; p = 0.049). Our findings have shown that GSTT1 null genotype might be a risk factor of CML in males. While, GSTT1 present genotype might be considered as protective against CML. However, further studies with a large sample size are needed to confirm our findings.

Acquired factor VII deficiency associated with acute myeloid leukemia.

Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

Primary splenic angiosarcoma revealed by bone marrow metastasis.

Primary splenic angiosarcomas are the most common malignant non-hematopoietic tumors of the spleen. Metastatic diseases were found in 69% of patients in a reported series but the incidence of bone marrow involvement is unclear. We report a rare case of a 25-years-old Moroccan woman with unsuspected primary splenic angiosarcoma revealed by bone marrow metastasis. She presented with serious anemia and splenomegaly. Bone marrow biopsy revealed proliferating spindle cells. Computed tomography scanning showed an enlarged spleen with heterogeneous lesions. Splenectomy was performed and retrospective histological study of the spleen confirmed the diagnosis. She died 1 year after splenectomy.

Naso-Sinusal T ALL With Aberrant Expression of CD56 Mimicking NK/T Non Hodgkin Lymphoma.

T-acute lymphoblastic leukemia (T-ALL) represents 25 % of cases of acute lymphoblastic leukemia (ALL) in adults. The clinical presentation is dominated by a elevated number of white blood cells and in immunophenotype the lymphoblasts are generally Tdt positive and variably express CD1a, CD2, CD3, CD4, CD5, CD7, and CD8. NK/T non Hodgkin lymphoma is presented as a single lesion often ulcerated with torpid evolution affecting the nasal cavity, nasopharynx and/or palate. CD56 expression is while characteristic of NK-cells, and is also expressed on a subset of normal T cells. Its expression in ALL does not exclude the diagnosis and seems to be a prognostic factor of this disease. We report the case of a young woman with nasal cavity tumor which was initially diagnosed as T-cell lymphoma. This diagnosis was finally revised to conclude to T-ALL with CD56 aberrant expression.

[Healthcare-associated infections in a paediatric haematology/oncology unit in Morocco]. / Infections associées aux soins dans une unité d'hématologie-oncologie pédiatrique au Maroc.

OBJECTIVE: HAI cause considerable morbidity and mortality and are associated with prolonged hospital stay and increased health care costs. To describe the incidence of HAI in paediatric cancer patients as the first step towards improving infection control policies. METHODS: A prospective surveillance study was performed in the Casablanca university hospital paediatric haematology/oncology unit over an 8-month period from January to August 2011. Data including extrinsic risk factors associated with HAI were recorded. RESULTS: The incidence of HAI was 28 per 1000 patient-days. The median age was 9.6 years and the most frequent diagnosis was acute myeloid leukaemia (32%). Neutropenia at diagnosis was significantly correlated with the risk of HAI. 55.7% of HAls were nosocomial fever of unknown origin. Gram-negative bacteria were the main pathogens (60%), gram-positive cocci were responsible for 26% of HAI and Candida for 14% of HAI. The length of hospital stay for patients with and without infection were 16.5 and 5 days, respectively (P < 0.001). Six of the 11 deaths were related to HAI. CONCLUSION: These findings suggest the need to evaluate infection control measures in order to reduce morbidity and mortality in paediatric haematology/oncology units.

Primary plasma cell leukemia presenting as a thoracic mass.

Primary Plasma cell leukaemia (pPCL) is a rare plasma cell (PC) malignancy. The strict criteria for the diagnosis is an absolute PC number greater 2 × 10(9)/L or a plasmocytosis accounting for > 20% of the differential white cell count that does not arise from a pre-existing multiple myeloma. pPCL was associated with aggressive clinic-biological features. Primary Plasma cell leukaemia is more characterised by an extra medullar involvement such as hepatomegaly, splenomegaly, lymphadenopathy, lepto-meningeal infiltration or extramedullary plasmocytomas. The prognosis of pPCL is very poor. We report the case of a fifty eight year-old man directed to the haematology department for diagnosis of pPCL revealed by a thoracic plasmocytomas mimicking a thoracic neoplasm. The patient received chemotherapy including a classic treatment for multiple myeloma but developed a pulmonary embolism. This case illustrates an uncommon presentation of pPCL the difficulty treating by multiple myeloma chemotherapy.

Functional polymorphism of CYP2B6 G15631T is associated with hematologic and cytogenetic response in chronic myeloid leukemia patients treated with imatinib.

In the spite of the impressive results achieved with imatinib in chronic myeloid leukemia (CML) patients, differences in patient's response are observed, which may be explained by interindividual genetic variability. It is known that cytochrome P450 enzymes play a major role in the metabolism of imatinib. The present study aimed to understand the functional impact of CYP2B6 15631G>T polymorphism on the response of imatinib in CML patients and its relation to CML susceptibility. We have genotyped CYP2B6 G15631T in 48 CML patients and 64 controls by PCR-RFLP. CYP2B6 15631G>T was not found to be a risk factor for CML (OR 95 % CI, 1.12, 0.6-2, p > 0.05). Hematologic response loss was higher in patients with 15631GG/TT genotype when compared with 15631GT (36.8 vs. 13.8 %; X (2) = 3.542, p = 0.063). Complete cytogenetic response was higher in 15631GG/GT genotype groups when compared with 15631TT (X (2) = 3.298, p = 0.024). Primary cytogenetic resistance was higher in patients carrying 15631GG/TT genotype when compared with 15631GT carriers (52.6 vs. 17.2 %; X (2) = 6.692, p = 0.010). Furthermore, side effects were more common for patients carrying 15631GG genotypes when compared with GT/TT carriers (36 vs. 13.8 %; X (2) = 8.3, p = 0.004). In light of our results, identification of 15631G>T polymorphism in CML patients might be helpful to predict therapeutic response to imatinib.

Hematopoietic stem cell transplantation practice variation among centers in the Eastern Mediterranean Region (EMRO): Eastern Mediterranean Bone Marrow Transplantation (EMBMT) group survey.

INTRODUCTION: This practice survey is conducted to analyze clinical hematopoietic stem cell transplantation (HSCT) practice variability among centers in the WHO Eastern Mediterranean Region (EMRO), as represented by the Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) group. METHOD: This internet based survey was completed by the medical program directors of the EMBMT centers; 17 centers participated. The survey collected data on various clinical aspects of HSCT practice. RESULTS: Consistency in pre HSCT cardiac (100%), pulmonary (82%) and viral screen (100%) was observed. Obtaining informed consent was universal. Pre-HSCT psychological assessment is practiced in 50% of the centers. All centers used single-bedded rooms with HEPA filters. Visitor policy during neutropenic phase and the use of gowns, masks or gloves when examining patients varied among centers. MRSA/VRE screen and use of low bacterial diet were applied in 65% and 82%, respectively. Anti-bacterial prophylaxis is employed in 58% (Auto-SCT) and 60% (Allo-SCT) of the centers. Drug choice varied (cotrimoxazole, ciprofloxacin, levofloxacin, piperacillin-tazobactam); 60% of the centers used penicillin prophylaxis in GVHD patients. PCP prophylaxis is applied in 58% (Auto-SCT) and 87% (Allo-SCT) of the centers; cotrimoxazole is usually used. Anti-viral prophylaxis with acyclovir or, less commonly, valacyclovir is used in 70% (Auto-SCT) and 93% (Allo-SCT) of centers. Anti-fungal prophylaxis is applied in 70% (Auto-SCT), 93% (myeloablative Allo-SCT) and 87% (reduced intensity [RIC] Allo-SCT). Fluconazole is used in all Auto-SCT and majority of Allo-SCT recipients; few centers used other agents (itraconazole, voriconazole, amphotericin B) in Allo-SCT. Prophylactic GCSF use varied among centers: Auto-SCT 77%, myeloablative Allo-SCT 33%, RIC Allo-SCT 27%. Use of ursodeoxycholic acid for venoocclusive disease (VOD) prophylaxis is variable: 60% (Allo-SCT) and 12% (Auto-SCT). Cyclosporine/methotrexate is the most commonly used GVHD prophylaxis in myeloablative Allo-SCT (93%); heterogeneity was seen in RIC SCT. Treatment of steroid refractory acute GVHD varied (ATG 53%, higher steroid dose 40%). CMV monitoring varied between antigenemia (53%) and PCR (40%) techniques. Pre-emptive anti CMV therapy is used in 86% of the centers, while 7% used routine CMV prophylaxis; 7% had no specific CMV management policy. CONCLUSION: Consistency was observed in areas of pre-SCT work up, use of single rooms, HEPA filters and GVHD prophylaxis. Heterogeneity is observed in other practice aspects including other isolation measures, anti-microbial prophylaxis, VOD prophylaxis, growth factor use and treatment of steroid refractory GVHD. Further studies are needed to probe the impact of such practice variations on post-transplant outcome and to ascertain the best clinical practice approach.

Improving the prognosis of pediatric Hodgkin lymphoma in developing countries: a Moroccan Society of Pediatric Hematology and Oncology study.

BACKGROUND: The event-free survival (EFS) of children with Hodgkin lymphoma (HL) exceeds 80% in high income countries (HIC), but little is known about this rate in developing countries. PROCEDURE: A prospective national protocol for children with classical HL was implemented in Morocco to increase EFS by careful risk stratification, providing each cycle of therapy on time, decreasing treatment abandonment, improving communication among healthcare providers, and improving data collection. Patients were stratified into a favorable risk group (Ann Arbor stages I and II, no B symptoms, no bulky disease, and no contiguous (E) lesions) and received four cycles of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) or an unfavorable risk group (all others) who received two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) and four cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP). All patients received involved-field radiotherapy 25.5 Gy after completion of chemotherapy. EFS was calculated counting death, relapse/resistant disease, and abandonment as events. RESULTS: From February 2004 to December 2007, 160 patients enrolled; 138 (86%) had unfavorable risk features. Twenty patients (12.5%) abandoned treatment, 16 relapsed or had resistant disease, and 6 died (3 unexplained, 2 varicella, and 1 suicide). The estimated 5-year EFS was 70 ± 4% and overall survival 88 ± 3%. CONCLUSIONS: Good outcomes for pediatric HL patients can be achieved in LMIC using a multidisciplinary team approach, uniform protocol-based therapy, twinning partnership among oncology units in-country and abroad, and a data collection system to monitor compliance and identify gaps in care.

Extramedullary plasmocytoma relapsing at differents sites: an unusual presentation.

Extramedullary plasmacytoma (EMP) is an uncommon plasma cell neoplasm results from plasma cell proliferation and consists of monoclonal plasmacytic infiltration, without bone marrow involvement and any other systemic characteristics of multiple myeloma. EMP accounts for 3% of all plasma cell neoplasms and approximately 80% to 90% of EMP involve submucosa of the upper aerodigestive, while scrotal, dermis and retroperitoneal infiltration are very rare. There are no consensus guidelines for treatment, but EMP is highly radiosensitive, surgery may be considered for some sites, but 11 at 30% can progress in multiple myeloma. We report here an exceptional case of recurrent EMP in much localization. It's about a man 72 years old with initially testicular plasmocytoma who generalized the plasmacytic infiltration after 16 months in skin and progressively in mediastinal and retroperitoneal plasmacytoma, without any medullar and bone involvement.

Infections in hospitalized children and young adults with acute leukemia in Morocco.

BACKGROUND: Overall survival from leukemia is less in low and middle-income countries than in high-income countries. Our purpose was to describe the incidence, clinical features, and mortality of febrile illness with or without documented infection in children and young adults treated for AML and ALL in two centers in Rabat and Casablanca during 2011. METHODS: This retrospective cohort study included patients <30 years of age who were newly diagnosed with AML and ALL in 2011 in Casablanca and Rabat. Each patient's chart was evaluated for patient demographics, febrile episodes, chemotherapy regimen, and clinical or microbiological evidence of infection, neutropenia, antibiotics, and mortality. RESULTS: One hundred sixty-six evaluable patients had 228 inpatient febrile episodes. The median number of febrile episodes in AML was three per patient, and for ALL, one per patient. Clinically identified infections mainly included pneumonitis and mucositis. Coagulase negative staphylococcus was the most commonly isolated bacterium, followed by gram-negative bacteria. Fifty-three percent of febrile episodes were classified as fever of undetermined origin. Broad-spectrum antibiotics were routinely used, with the addition of antifungals in 62 episodes and vancomycin in 83 episodes. The rate of deaths per febrile illness was 11.3% (16/141) in patients with AML, and 9.2% (8/87) in patients with ALL. CONCLUSION: The higher rate of infectious deaths in leukemia compared to that reported in high-income countries, suggests that improvements in infection care and prevention, including consistent access to rapid hospitalization, diagnostics and antibiotics; and standardizing quality of patient care are necessary to improve as well as survival in patients with leukemia in Morocco.

Immunohistochemical expression of CD44s in human neuroblastic tumors: Moroccan experience and highlights on current data.

BACKGROUND: Peripheral neuroblastic tumors (pNTs), including neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN), are extremely heterogeneous pediatric tumors responsible for 15 % of childhood cancer death. The aim of the study was to evaluate the expression of CD44s ('s': standard form) cell adhesion molecule by comparison with other specific prognostic markers. METHODS: An immunohistochemical profile of 32 formalin-fixed paraffin-embedded pNTs tissues, diagnosed between January 2007 and December 2010, was carried out. RESULTS: Our results have demonstrated the association of CD44s negative pNTs cells to lack of differentiation and tumour progression. A significant association between absence of CD44s expression and metastasis in human pNTs has been reported. We also found that expression of CD44s defines subgroups of patients without MYCN amplification as evidenced by its association with low INSS stages, absence of metastasis and favorable Shimada histology. DISCUSSION: These findings support the thesis of the role of CD44s glycoprotein in the invasive growth potential of neoplastic cells and suggest that its expression could be taken into consideration in the therapeutic approaches targeting metastases. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1034403150888863

[A congenital α2-antiplasmin deficiency]. / À propos d'un déficit constitutionnel en α2-antiplasmine.

Α 2 antiplasmin congenital deficiency is an uncommun fibrinolysis disorder that is diagnostics after a post-operative surgery. We report two brothers cases of α 2 antiplasmin deficiency diagnosed after a prostadenomectomy bleeding at two years intervals.

[Reccurent pregnancy loss and 20210GA prothrombin mutation]. / Fausses couches à répétition et mutation 20210GA de la prothrombine.

Prothrombin mutation, in the same way as the factor V Leiden, is a thrombophilic state susceptible to induce both thrombosis and repetition of miscarriages at pregnancy woman. We report a case of 36 year-old woman who presented two miscarriages leaded to thrombophily state diagnosis by prothrombin mutation and among which two last pregnancies were led to their term thanks to anticoagulation.