Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients.

Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n = 749) or at the end (n = 635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT: 5.7% vs 5.8%, P = .98; 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n = 1253). In patients with a high CNS international prognostic index (n = 600), the 3-year CNS relapse rate was 9.1%, with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with a reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX vs EOT, with 308 of 1573 (19.6%) i-HD-MTX treatments resulting in a delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk vs i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.

Salvage therapy with brentuximab-vedotin and bendamustine for patients with R/R PTCL: a retrospective study from the LYSA group.

Patients with relapsed or refractory (R/R) peripheral T-cell lymphomas (PTCL) have a poor prognosis. Bendamustine (B) and brentuximab-vedotin (Bv) have shown interesting results in this setting. However, little information is available about their efficacy in combination. This multicenter and retrospective study aimed to evaluate the efficacy and safety of the combination of BBv in patients with noncutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was the overall response rate. A total of 82 patients with R/R PTCL were included. The best overall response rate (ORR) was 68%, with 49% of patients in complete response (CR). In multivariable analysis, only the disease status after the last regimen (relapse vs refractory) was associated with the response with an ORR of 83% vs 57%. Median duration of response was 15.4 months for patients in CR. With a median follow-up of 22 months, the median progression free survival (PFS) and overall survival (OS) were 8.3 and 26.3 months respectively. Moreover, patients in CR, who underwent an allogeneic transplant, had a better outcome than patients who did not with a median PFS and OS of 19.3 vs 4.8 months and not reached vs 12.4 months, respectively. Fifty-nine percent of patients experienced grade 3/4 adverse events that were mainly hematologic. BBv is highly active in patients with R/R PTCL and should be considered as a one of the best options of immunochemotherapy salvage combination in this setting and particularly as a bridge to allogeneic transplant for eligible patients.

Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life-experience of the French Network.

We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.

Intrauterine Growth Retardation Complicated by Biermer's Disease: An Observation in Togo.

OBJECTIVE: To report the first case in Togo of Biermer's disease associated with intrauterine growth retardation (IUGR) in a 39-year-old pregnant woman. OBSERVATION: The patient with phenotype AA, born on 20/02/1978, G2P0 (a spontaneous abortion at 3 months), was referred to hematology on 17th March 2017 for anemia at 26 weeks of amenorrhea (WA). She had received martial treatment with ferrous fumarate 66 milligrams daily. At 26 weeks, the uterine height was 16 centimeters, and there was good fetal vitality. During ultrasound, there was a harmonious development of the fetus, but it was lower than that for the gestational age at 10th percentile based on fetal biometry, and anemia was at 65 g/l. She was then referred to hematology where she was found to have pancytopenia with macrocytic aregenerative anemia at 47 g/l (MCV at 109 fl), neutropenia at 1.02 g/l, and thrombocytopenia at 58 g/l. The myelogram found megaloblastosis at 53%, collapsed serum B12 vitamin at 61.7 pg/ml, normal serum folate at 9.9 ng/ml, increased serum homocysteine to 51.44 µmol/l, and elevated LDH. The search for intrinsic anti-factor antibodies was positive. Digestive endoscopy noted fundal atrophy. The patient was given vitamin B12 injection; at the 7th day, hemoglobin was observed at 94 g/l, then a normalization of the blood count after 3 weeks, and a good evolution of the pregnancy with delivery at 38 WA of a newborn, female, weighing 1960 g with 500 grams of placenta, with a size of 40 cm, and a cranial perimeter of 29 cm. The child had stunted weight growth (at 16 months; weight = 7 kg; height = 69 cm). CONCLUSION: Biermer's disease as a maternal cause of IUGR and infantile hypotonia is a reality in Togo. It requires management in patients and especially during pregnancy to avoid neurological complications in children born from mothers with this disease.

[Characteristics of chronic lymphocytic leukemia in Togo]. / Caractéristiques de la leucémie lymphoïde chronique au Togo.

The epidemiological, clinical and biological characteristics of chronic lymphocytic leukemia (CLL) are little studied in Togo. The purpose of this study was to describe these characteristics at the time of diagnosis. We conducted a retrospective and descriptive study of patients diagnosed at the University Hospital Campus from January 1999 to December 2018. Over the past two decades, 87 patients were seen for CLL (20% of patients with hematological malignancies) with an annual prevalence of 4.35 new cases. The average age of patients was 61 +/- 12,48 years (ranging from 17-85 years); 55 women and 32 men (sex ratio M/F 0.58) were enrolled. Clinically, 16 patients (18%) had no tumor syndrome, 33 patients (38%) had lymphadenopathy, 62 patients (71%) splenomegaly and 23 patients (26%) hepatomegaly. Biologically, the mean blood and medullary lymphocyte count was 87188/mm3 (ranging from 7000-481780/mm3) and 75.75% +/- 12,88 (ranging from 44,5-96,5%) respectively; 65 patients (75%) had haemoglobin less than 10g/dl and 20 patients (23%) had platelet count below 100000/mm3. At the time of diagnosis, 67 patients (77%) had Binet stage C, 7 patients (8%) stage B and 13 patients (15%) stage A. The study of biological prognostics factors showed that 66% of cases had ß2-microglobulin level higher than normal and 95% of cases had LDH higher than normal. CLL is a reality in Togo with a predominance of women and an average age of 61 years. Most patients are seen at Binet stage C and their assessment has revealed huge tumor mass with increased LDH and ß2-microglobulin. The current follow-up of these patients will enable us to assess their overall survival.

[Types of bcr-abl and their correlations with the blood count in chronic myeloid leukemia (CML) in Togo]. / Les transcrits bcr-abl et leurs corrélations avec l'hémogramme au cours de la leucémie myéloïde chronique (LMC) au Togo.

This study aims to describe the different bcr-abl gene transcript variants in order to determine their frequency and to study their influence on CBC diagnostic test. We conducted a cross-sectional study of 34 patients with chronic myeloid leukemia in Togo. The search for fusion transcripts was performed in the laboratory of biological haematology at the Henri Mondor Hospital, Créteil (France). The average age of patients was 42,32±14,87 years ranging between 9 and 65 years. Most patients were male, with a sex- ratio of 1.61 (21 men and 13 women). Molecular examination showed b3-a2 transcript and b2-a2 transcript. Nineteen patients (55.88%) expressed b3-a2 transcript, 13 patients (38.24%) b2-a2 transcript (32.10%) and two patients expressed both b3-a2 and b2-a2 transcripts (5.88%). At diagnosis, mean hemoglobin level, the average number of white blood cells and the average number of platelets in patients expressing b3-a2 transcript were 99,2g/L; 207,63g/l and 451,28g/l respectively. In patients expressing b2-a2 transcript values were 104,6g/l, 114,32g/l and 486,11g/l. In patients with both transcripts, values were 67g/L, 867g/l and 780g/l respectively. CBC parameters are more significantly altered in patients with both transcripts b3-a2 and b2-a2.

[Myeloproliferative disorders "Philadelphia negative" and JAK2V617F mutation: study of 15 cases in Togo]. / Syndromes myéloprolifératifs « Philadelphie négatif ¼ et mutation JAK2V617F : étude des 15 premiers cas ayant bénéficié de cette recherche au Togo.

The goal of our study is to document the prevalence of change JAK2V617F among patients reached of myeloproliferative syndromes (MPS) in Togo in order to evaluate frequencies. This descriptive study included 15 patients followed with the CHU Campus for a SMP. The research of JAK2 change by PCR was carried out with the APHP Henri Mondor of Creteil (France). During the study period, 15 patients followed for MPS (9 cases of polycythemia Vera, 5 cases of essential thrombocytemia and a case of primitive myelofibrosis) profited from the research of JAK2 change. The Middle age of the patients was respectively of 45±18 years; of 55±6 years for the PV and the essential thrombocytemia. The patient followed for primitive myelofibrosis was 72 years old. Sex-ratio (H/F) was of 2. JAK2 Change was positive in 5 cases out of 9 (55.5%) of the polycythemia Vera, at 3 patients out of 5 (60%) followed for essential thrombocytemia but negative for patient reached of primitive myelofibrosis. In conclusion, JAK2 Change has an interest diagnosis and forecast in the MPS negative Chromosom Philadelphia and can be systematic even in Africa Sub-saharian.

Clonal hypereosinophilic syndrome: two cases report in black men from sub-saharan Africa and literature reviews.

The first case is about a man of 60 years old suffering of hypereosinophilic syndrome (HES) developed since 1998. He presented chronic cough, insomnia, and negative parasitical test. We observed hypereosinophilia and fibroblastic hyperplasia at the bone marrow biopsy. Initially, hydroxyurea and α-interferon treatment failed. We proposed to him imatinib mesylate in May 2003. The FIP1L1-PDGFRA gene was detected. The second case is about a man of 34 years old seen in March 2002. First investigation concluded to CML. Progressively, eosinophil cells increased, and complications occurred as oedema syndrome, dyspnoea, and parietal chronic endocarditic fibrosis associated with pericarditis. In addition, a bowel obstruction happened and was cured by surgery. Bcr-abl fusion was negative, and FIP1L1-PDGFRA gene was detected after and imatinib mesylate was given. Actually, endocarditic fibrosis decreased. The two patients are in haematological and cytogenetic remission. We concluded that clonal HES is present in Africa, and imatinib mesylate is effective.