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.

[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.

[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.

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.

Drug administration error related to computerized prescribing.

INTRODUCTION: One of the main reasons for the implementation of computer-based prescribing was to reduce medication errors. However, the risk has not fallen to zero and new kinds of errors have been detected. SETTING: the following case relates one of these medication errors involving a preparation of vincristine. This antineoplastic drug was injected to a patient via a subcutaneous route of administration instead of an intravenous bolus injection. RESULTS: consequently, a cutaneous erythema appeared. This incident resulted from an error in the programming of the administration route of the protocol operated by a pharmacist and a physician. The pharmacist, who was responsible for the validation of the computerized medical order and then for the compounding and the dispensing of the drug, did not detect the error. CONCLUSION: this case highlights the need of improved and irreproachable therapeutic protocols. Recorded in a database, they must be validated pharmaceutically and medicinally to secure computer-based prescribing, drug handling, dispensing, and administering of the antineoplastic drugs. Even if the pharmaceutical analysis of prescriptions is made easier with computerization, we encourage the training of nurses and the evaluation of their knowledge as well as the necessity for pharmacists to learn to detect new kinds of errors and to verify periodically protocols.

[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.

[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.

[Radiotherapy in stage I testicular seminoma: retrospective study and review of literature]. / Radiothérapie des séminomes testiculaires de stade I : étude rétrospective et revue de la littérature.

INTRODUCTION: Seminoma accounts for about 40% of germ cell tumours of the testicle. In this retrospective analysis, we review literature concerning management of stage I seminoma. MATERIALS AND METHODS: Between March 1987 and April 2001, 65 patients with stage I pure testicular seminoma received adjuvant radiotherapy with a 25 MV linear accelerator. RESULTS: Median age was 33 years. Testicular tumour has been found on the right testis in 39 patients and on the left one in 24 patients. Patients have been treated using an anterior-posterior parallel pair and have received 20-25 Gy in 10-14 fractions. The target volume consisted of paraaortic, and paraaortic + homolateral iliac lymph nodes in 17 and 46 patients, respectively. Acute toxicity was mainly digestive, 38% of patients presenting nausea and vomiting. Median follow-up time was 37 months. All patients are alive in complete remission. DISCUSSION: Because of good radio-sensitivity of seminoma, radiotherapy is regarded as standard adjuvant treatment (5 years relapse rate: 3-5%). Acute toxicity is dominated by moderate gastro-intestinal side effects. Secondary neoplasia represents one of the worst possible long-term complications of therapy. Waiting for ongoing randomised trials, the modern literature for seminoma reflects a trend toward lower radiation doses (20-25 Gy) and smaller treatment volumes (paraaortic field). Adjuvant chemotherapy with two courses of carboplatin, might be equivalent to radiotherapy but must be investigated in randomised trials. A surveillance policy is one of the other management options less recommended.

[Myeloid pseudo-splenomegaly in a patient with a myeloma]. / Pseudo-splénomégalie myéloïde chez un patient ayant un myélome.

INTRODUCTION: Lymphoproliferative syndromes are rarely complicated by medullar fibrosis simulating myeloid splenomegaly. OBSERVATION: We report an unusual case of an IgD myeloma revealed in a context of myeloid splenomegaly in a 37 year-old man, initially admitted for severe anaemia associated with a voluminous splenomegaly. COMMENTARIES: The occurrence of myeloid splenomegaly during myeloma is extremely rare and only 14 cases have been reported. In this context, myelofibrosis is secondary to plasmocyte invasion of the bone marrow and regresses, or disappears, following specific treatment of the myeloma. The hypothesis evoked to explain the appearance of a secondary myelofibrosis is the "inappropriate" secretion, by the malignant plasmocyte clone, of functional analogs of pro-fibrosis cytokines, usually secreted by the mega-caryocyte precursors implied in myeloid splenomegaly.

[Secondary medullary aplasia from accidental radiation:therapeutic options and evolution of the concept]. / L'aplasie médullaire secondaire à un accident d'irradiation:options thérapeutiques et évolution des concepts.

Bone marrow grafting following accidental irradiation exposure should be viewed in the perspective of a severe myeloablative syndrome linked to high medullary damage for a dose range higher than 6-8 Gy, resulting in very late or no recovery. Prognosis will depend on the presence or absence of radio-combined injuries, the toxicity of the transplant procedure, and the risk of rejection induced by insufficient percritical immunosuppression. It is in this context that new cell therapy modalities, which combine enhanced peripheral hematopoietic cell engraftment and high immunosuppressive conditioning regimen with low extrahematological toxicity, inducing early and stable mixed lymphomyeloid chimerism with minimal morbidity, can be considered. Such an approach is being evaluated in the treatment of patients with hematological malignancies at high risk of transplant-related mortality using conventional bone marrow methods.

Dicentric chromosome 3 associated with binucleated lymphocytes in atypical B-cell chronic lymphoproliferative disorder.

Binucleated lymphocytes on blood smear are known in PPBL characterized by stable and polyclonal lymphocytosis, polyclonal increase of serum IgM, HLA DR7 and strong correlation with additional i(3q) and premature chromosome condensation. In this disorder some reports of clonal Ig rearrangement suggest a follow up of these patients with immunological and genetic studies. Binucleated lymphocytes are rarely described in other clonal B-CLPD as B-CLL or marginal zone B-cell lymphoma (MZL). Chromosome 3 abnormality is never described in B-CLL but trisomy 3 represents the most consistent abnormality characterizing the MZL. We report in a man without previous medical history an unusual B-CLPD with monoclonal lymphocytosis CD5-, characteristic cytology (particularly binucleated lymphocytes) and chromosomic abnormality as dicentric chromosome 3 never previously described in B-CLPD. In this case lymphocytosis is persistent and stable over 24 months, cytologic immunologic and chromosomic abnormalities are unchanged. We discuss the nosologic place of this atypical B-CLPD closely related to PPBL and MZL with at the moment, after 24 months, a quiet evolution that imply nevertheless a careful follow up with regular cytologic, immunological and genetic studies to clarify the issue.

Assessing the Cox model assumption as a statistical tool for classifying lymphomas.

INTRODUCTION: The Cox model is widely used in medical research for comparing survival. Lymphomas might exhibit important differences in long-term cure rate despite a similar survival. METHODS: Using log-rank test, we compared event-free survival (EFS), and the survival of 64 patients with mantle cell lymphoma (MCL), 525 patients with follicular lymphoma, and 1136 patients with diffuse centroblastic lymphoma (CB). RESULTS: Although EFS and survival of MCL were significantly shorter than those of follicular lymphoma, checking the validity of the proportional hazards assumption shows that the distribution of rates of events and deaths over time did not differ in MCL and follicular lymphoma. In contrast, the ratios of hazards (events and deaths rates) did not remain constant over time in MCL and CB, because of a decrease in late events and deaths rates in the latter histological type. CONCLUSION: Checking the validity of the Cox model hypothesis might be a useful tool for assessing long-term cure rate in seldom lymphoma subtypes. Despite a short overall survival, MCL should not be considered to be an aggressive lymphoma, in which available chemotherapy may cure a subset of patients.

Real-time quantitation of bcr-abl transcripts in haematological malignancies.

We have applied an automated real-time quantitative PCR assay using a double-labeled fluorogenic probe to detect t(9;22)-positive cells in haematological malignancies. The results are expressed as the ratio of chimeric bcr-abl transcripts on abl transcripts. Highly reproducible results were obtained for t(9;22)-positive K562 RNA. Ten copies of bcr-abl DNA from a recombinant KW-3 plasmid and one positive cell in 10(4) can be detected. Thirty-two patients with chronic myeloid leukaemia (CML), 25 with acute leukaemia, 12 with myelodysplastic syndromes and 7 with other myeloproliferative syndromes were tested. Follow-up data were obtained in bcr-abl positive cases. Results were compared with those of conventional nested RT-PCR and cytogenetics. Real-time quantitative RT-PCR values correlated well with both these methods. However, in some cases the only means of detecting early relapse or blastic transformation was to examine the kinetics of real-time quantitative RT-PCR. Thus, real-time quantitative RT-PCR appears suitable for the diagnosis and follow-up of patients with the t(9;22) translocation.

Efficacy of autologous stem cell transplantation in mantle cell lymphoma: a 3-year follow-up study.

This study was designed to evaluate the efficacy of therapeutic intensification with autologous stem cell transplantation (ASCT) for mantle cell lymphomas (MCL) in terms of response rate, duration of response, and event-free and overall survivals. Twenty-four patients with confirmed MCL responding to chemotherapy received a high-dose chemo-radiotherapy regimen followed by ASCT. Transplantation was performed during first-line therapy in nine cases, second-line in 13 cases and third-line in two cases. The source of hematopoietic stem cells was peripheral blood for 19 cases. At the time of ASCT, eight patients were in complete remission (33%). Seventeen of the 24 cases received an intensified regimen with TBI and seven received the BEAM or the BEAC regimen. After transplantation, 19 patients were in CR (79%). Nine of these were alive in continued CR at a median follow-up of 34 months, while seven relapsed at a median of 18 months. One patient died from Pneumocystis carinii interstitial pneumonitis and five patients developed secondary malignancies. With a median follow-up after transplantation of 34 months, the 3-year event-free survival was 55% and the 3-year overall survival was 68%. These results indicate that therapeutic intensification with ASCT might be an effective treatment for mantle cell lymphomas. Bone Marrow Transplantation (2000) 25, 251-256.

European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma.

PURPOSE: Mantle-cell lymphoma (MCL), immunocytoma (IMC), and small B-cell lymphocytic lymphoma (SLL) are B-cell malignancies that express CD20 and are incurable with standard therapy. A multicenter phase II study was conducted to assess the toxicity and the overall response rates (RR) and complete response (CR) rates to rituximab (chimeric anti-CD20 monoclonal antibody). PATIENTS AND METHODS: Between January 1997 and January 1998, 131 patients with newly diagnosed MCL (MCL1; n = 34) and previously treated MCL (MCL2; n = 40), IMC (n = 28), and SLL (n = 29) received rituximab 375 mg/m(2)/wk for 4 weeks via intravenous infusion. Restaging studies were performed 1 and 2 months after treatment. An analysis of the duration of response was conducted in December 1998. RESULTS: Eleven patients were unassessable, including one who died of splenic rupture after the first infusion. The RR among the 120 assessable patients was 30% (36 of 120 patients). The RR by histology was as follows: MCL1, 38%; MCL2, 37%; IMC, 28%; and SLL, 14%. Ten patients, all with MCL, achieved CR. The median duration of response in MCL was 1.2 years. Immediate side effects were common and usually responded to adjustments in the infusion rate. There were 31 episodes of infection after treatment; most cases were mild. Cardiac arrhythmia and ophthalmologic side effects occurred in 10 and nine patients, respectively, including one case of severe loss of visual acuity. CONCLUSION: Single-agent rituximab has moderate activity in MCL and IMC but only limited activity in SLL. The duration of response in MCL was similar to that previously reported in follicular lymphoma. Its use in combination with cytotoxic chemotherapy to increase the CR rate is warranted in MCL and IMC.

[Treatment of thrombotic microangiopathies]. / Traitement des microangiopathies thrombotiques.

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome appear as the same expression of thrombotic microangiopathy (TMA), which is a single pathological entity affecting small blood vessels leading to hemolytic anemia, circulatory changes with renal (hemolytic uremic syndrome, HUS) or nervous (thrombotic thrombocytopenic purpura, TTP) involvement. Because of his low incidence, prospective randomized clinical trials are difficult to conduct and apart from plasma exchanges (PE) which appear superior to plasma infusions (PI), other therapeutic recommendations are based on retrospective studies or on anecdotal reports with limited number of patients. In the absence of appropriate therapy, mortality rate was initially above 90% in adults with TTP. Plasma infusions and plasma exchanges have dramatically improved prognosis of the disease, since more than 80% of patients respond to therapy with a survival greater than 80 to 90%. Analysis of data of medical literature shows that plasma exchanges can cure 82% of TMA with 15% of refractory TMA and a mortality rate of 14%. In two randomized trials, PE are more effective than PI with a response rate benefit of 25% and an overall survival increase of 15%. Although severe thrombocytopenia is frequently observed, it is important to avoid platelet transfusions. Platelets infusions induce deleterious effects since they add to the severity and the extend of microvascular thrombi formation. Use of glucocorticoids, heparin, antiplatelet therapy, intravenous immunoglobulin and vincristine are associated with variable results and no controlled study supports their use. Splenectomy is still under discussion but could be of interest in case of relapsing thrombotic microangiopathies as an attempt to reduce the rate of TMA recurrence.

Intensive chemotherapy with hematopoietic cell transplantation after ESHAP therapy for relapsed or refractory non-Hodgkin's lymphoma. Results of a single-centre study of 65 patients.

This study was designed to assess the results of protracted courses of ESHAP (etoposide, cytarabine, cisplatin, methylprednisolone) therapy followed by intensive chemotherapy and hematopoietic cell transplantation (IC+HCT) for relapsed or refractory non-Hodgkin's lymphoma (NHL). Treatment consisted of 3 cycles of ESHAP; responsive patients (pts) then received 3 more cycles, and IC+HCT was used for pts in maintained partial (PR) or complete (CR) remission after the sixth ESHAP. Sixty-five pts entered the study. At enrollment, 27 pts had bone marrow (BM) and/or central nervous system (CNS) lymphomatous infiltration. Disease status was primary refractory lymphoma in 41 pts (63 %), and relapse in 24 pts (37 %). Results showed that two pts were not evaluable for the therapeutic response because of early treatment-related death. Thirty-nine (62 %) pts entered PR or CR after 3 cycles of ESHAP. Eleven pts subsequently had disease progression. Twenty-eight pts were in persistent CR or PR after 6 cycles of ESHAP. Refractory pts did not show a different response rate to relapsing pts (chi2= 1.73). Five pts were excluded from IC+HCT because of an inadequate graft or treatment-related toxicity. Twenty-three (35 %) pts completed the procedure. Five pts (22 %) relapsed after IC+HCT. The overall survival rate of the 39 responsive pts is 45 % at 60 months, with a median survival time of 30 months. Median survival among the 35 pts in whom second-line chemotherapy failed is 7.1 months, with a 4-year survival rate of 3 %. Despite the poor prognostic features of this group, 45% of pts responding to the first 3 cycles of chemotherapy are in prolonged remission, suggesting that rather than to transplant after just 2 cycles of salvage therapy, pursuing second-line chemotherapy may better discriminate between patients more likely to benefit from a subsequent transplant.