G. Garnier

Ticlopidine and severe aplastic anaemia.

positive for CDI 3 . CD3 3 and HLA-DK. with CD34 expression occurring in all but one patient (Table I). Cytogenetic analysis was abnormal in all patients, although no single abnormality prevailed (Table I). No patient gave a history of suspicious chemical or toxin exposure. Three patients received standard MKC-AML 10 or 11 trial chemotherapy. two received a similar anthracycline, cytosine combination while the sixth. on account of age, received subcutaneous cytosine and oral thioguanine only. Two patients entered remission, one lasting 2 years before relapsing with resistant disease, while the second is alive and well 7 months post AML 10 chemotherapy (without ABMT). All four patients who failed to enter remission died within 10 weeks of presentation. It is noteworthy that the patient who is alive at 7 months entered remission after one course of chemotherapy (DAT 3 + 10). was negative for CD34 and had the lowest white cell count at presentation. Interestingly, CD34 expression has been shown to have independent prognostic significance in AML and is associated with resistance to remission induction chemotherapy (Geller et al, 1990). In conclusion, our experience with AML-MO. albeit small, reveals certain trends: ( i ) poor remission rates with associated poor survival, ( i i ) a high incidence ofcytogenetic abnormality (lOOO/,). and ( i i i ) most cases express CD34. Clearly additional patients need to be studied to contirm these tindings, and also

Caloric restriction modulates Mcl-1 expression and sensitizes lymphomas to BH3 mimetic in mice.

Caloric restriction (CR) is proposed to decrease tumorigenesis through a variety of mechanisms including effects on glycolysis. However, the understanding of how CR affects the response to cancer therapy is still rudimentary. Here, using the Eµ-Myc transgenic mouse model of B-cell lymphoma, we report that by reducing protein translation, CR can reduce expression of the prosurvival Bcl-2 family member Mcl-1 and sensitize lymphomas to ABT-737-induced death in vivo. By using Eµ-Myc lymphoma cells lacking p53, we showed that CR mimetics such as 2-deoxyglucose led to a decrease in Mcl-1 expression and sensitized lymphoma cells to ABT-737-induced death independently of p53. In keeping with this, Eµ-Myc lymphoma cells lacking the BH3-only proapoptotic members Noxa, Puma, or Bim were also sensitized by CR mimetics to ABT-737-induced death. Remarkably, neither the loss of both Puma and Noxa, the loss of both Puma and Bim, nor the loss of all three BH3-only proteins prevented sensitization to ABT-737 induced by CR mimetics. Thus, CR can influence Mcl-1 expression and sensitize cells to BH3 mimetic-induced apoptosis, independently of the main BH3-only proteins and of p53. Exploiting this may improve the efficiency of, or prevent resistance to, cancer therapy.

High-dose chemotherapy with carmustine, etoposide, cytarabine and melphalan followed by autologous stem cell transplant is an effective treatment for elderly patients with poor-prognosis lymphoma

Autologous stem cell transplant (ASCT) after high-dose chemotherapy (HDT) increases overall survival when used in relapsed non-Hodgkin lymphoma (NHL) in patients under 65 years old. Limited experience is available for older patients. We present a retrospective analysis of 73 consecutive patients aged over 65 years treated for aggressive or relapsed lymphoma by HDT with carmustine, etoposide, cytarabine and melphalan (BEAM) at full dosage followed by ASCT. Patient data were obtained from medical charts from two institutions. Median age was 67 years (65–74). Significant comorbidities were present in 24.7% of patients. The median number of days for grade 4 neutropenia was 9 (5–18). The early treatment-related mortality rate (< 100 days) was 2.7%. The estimated 2-year progression-free survival and overall survival rates were 67.2% and 78.5%, respectively. In conclusion, the full-dose HDT-ASCT regimen is feasible, safe and efficient in selected patients over 65 years old.

Monosomal karyotype improves IPSS-R stratification in MDS and AML patients treated with Azacitidine.

IPSS‐R classifies cytogenetic abnormalities into five prognostic groups for survival. Monosomal karyotype (MK) is not a subgroup of IPSS‐R. Additional prognostic information from MK in poor and very poor karyotype has been recently shown. The aim of our study was to determine the prognostic value of IPSS‐R and MK for response and survival in AZA‐treated high‐risk MDS and AML with 20–30% of blasts patients. The study population included 154 patients who were classified according to IPSS‐R. IPSS‐R was not predictive of response (intermediate, 64%; poor, 44%; very poor, 56%; P = 0.28) or survival (intermediate, 25 months; poor, 12 months; very poor, 11 months; P = 0.14). Twenty‐one patients (15%) presented with MK and had a median OS of 9 months. Patients with a very high IPSS‐R score without MK had a median OS of 15 months, while patients with a high IPSS‐R score without MK had a median OS of 13 months (P = 0.18). We reclassified patients into the following three groups to include MK status: very high (MK only; OS median: 9 months), high (very high IPSS‐R without MK and high IPSS‐R without MK; OS median: 14 months) and intermediate (OS median: 25 months). As in recent publication including MK prognostic, we confirmed that this classification was predictive for survival in AZA treated patients (P = 0.008). IPSS‐R failed to discriminate between the prognostic subgroups. Stratification with MK has value in the prognosis of our cohort of AZA‐treated patients. Am. J. Hematol. 88:780–783, 2013.

Neutrophilic dermatosis associated with chronic neutrophilic leukemia

Chronic neutrophilic leukemia is an uncommon myeloproliferative disorder. We report a new case that fulfills the clinical and biologic criteria for such a diagnosis. The hematologic disease was revealed by a neutrophilic dermatosis that finally disappeared spontaneously after a duration of 1 year. Despite the lack of parallelism in the course of dermatologic and hematologic manifestations, we believe they were strongly linked. Occurrence of neutrophilic dermatoses in the course of other myeloproliferative disorders is well known. However, in our case, clinical and histologic features could not be used to distinguish between atypical Sweets syndrome and specific cutaneous lesions because of the mature appearance of both skin and blood neutrophils.

MACOP-B Chemotherapy for the Treatment of High-Grade Lymphomas in Patients with HIV-1 Infection

Recent studies showed that patients with non-Hodgkins lymphoma (NHL) with human immunodeficiency virus type 1 (HIV-1) infection may benefit from an intensive chemotherapeutic regimen. We report on our experience in the treatment of NHL-associated HIV-1 infection, with excellent prognostic factors, with MACOP-B regimen.

Un cas de cryptococcose neuroméningée chez un patient non sidéen

Summary A case of meningitis due to cryptococcus was diagnosed in a 22 years old woman. The diagnosis was assessed by the presence of cryptococcus in the cerebrospinal fluid. The evolution was favourable with fluconazole therapy. There was no identified risk factor and particularly, the serology for HIV was always negative 29 months later.

BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia

Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic (MDS) patients can also improve overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, but reliable biological markers predicting response and OS in patients treated with AZA are lacking. In a preliminary study, we found that an increase of the percentage of BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA resistance. In this study, we assessed prospectively by flow cytometry the prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients (42 MDS and 28 AML), prior to AZA treatment. In patients with baseline marrow blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells inversely correlated with response to AZA and OS independently of the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R). Specifically, OS was significantly lower in patients with more than 10% BCL2L10 positive cells (median 8.3 vs 22.9 months in patients with less than 10% positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice.

Lymphome malin et polyarthrite rhumatoïde traitée par méthotrexate

It is actually possible that the mild immunosuppression that occurs with methotrexate therapy places patients with rheumatoid arthritis at added risk for developing lymphoproliferative diseases. So we describe a new case.

Infections opportunistes et lymphopénie CD4 chez des patients VIH+ traités par interféron pour hépatite C

We report 2 cases of CD4 lymphocytopenia complicated by opportunistic infections in HIV-positive patients treated with interferon for chronic C-hepatitis. We believe that such therapy in these patients needs to take into consideration clinical status, CD4 lymphocytes count, HLA antigen, and risk/benefit ratio.