Lauris Gastaud

Low-dose vemurafenib induces complete remission in a case of hairy-cell leukemia with a V600E mutation.

Hairy-cell leukemia (HCL) is a lymphoproliferative disorder characterized by the presence of CD103-positive circulating B cells, pancytopenia and splenomegaly.[1][1] HCL cases were recently shown to harbor a mutation at codon 600 of BRAF ( V600E ), suggesting that this genetic event represents a key

Bing-Neel syndrome, a rare complication of Waldenström macroglobulinemia: analysis of 44 cases and review of the literature. A study on behalf of the French Innovative Leukemia Organization (FILO).

Central nervous system involvement by malignant cells is a rare complication of Waldenström macroglobulinemia, and this clinicopathological entity is referred to as the Bing-Neel syndrome. There is currently no consensus on the diagnostic criteria, therapeutic approaches and response evaluation for this syndrome. In this series, we retrospectively analyzed 44 French patients with Bing-Neel syndrome. Bing-Neel syndrome was the first manifestation of Waldenström macroglobulinemia in 36% of patients. When Waldenström macroglobulinemia was diagnosed prior to Bing-Neel syndrome, the median time interval between this diagnosis and the onset of Bing-Neel syndrome was 8.9 years. This study highlights the possibility of the occurrence of Bing-Neel syndrome without any other evidence of progression of Waldenström macroglobulinemia. The clinical presentation was heterogeneous without any specific signs or symptoms. Biologically, the median lymphocyte count in the cerebrospinal fluid was 31/mm3. Magnetic resonance imaging revealed abnormalities in 78% of the cases. The overall response rate after first-line treatment was 70%, and the overall survival rate after the diagnosis of Bing-Neel syndrome was 71% at 5 years. Altogether, these results suggest that Bing-Neel syndrome should be considered in the context of any unexplained neurological symptoms associated with Waldenström macroglobulinemia. The diagnostic approach should be based on cerebrospinal fluid analysis and magnetic resonance imaging of the brain and spinal axis. It still remains difficult to establish treatment recommendations or prognostic factors in the absence of large-scale, prospective, observational studies.

Acute kidney injury following crizotinib administration for non-small-cell lung carcinoma

A case of locally advanced non-small-cell lung carcinoma (NSCLC) was inadequately controlled with cisplatin, bevacizumab and pemetrexed chemotherapy. Following identification of a mutation of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene, crizotinib was then administered as targeted treatment. Kidney function was normal at diagnosis and during the first line therapy. The administration of crizotinib coincided on two occasions with a conspicuous rise in the serum creatinine level. Urinary protein over creatinine ratio was 0.31 g/g with 22% albumin and macroscopic hematuria. A kidney biopsy was performed at the time of the second episode of renal impairment which showed acute tubular necrosis (ATN) indicating recent renal injury together with a mononuclear cell infiltrate consistent with ongoing repair related to a previous insult. The renal lesions were closely related temporally to crizotinib administration, supporting a causative role for crizotinib in the acute renal injury and this phenomenon has not previously been described.

FDG-PET/CT is a pivotal imaging modality to diagnose rare intravascular large B-cell lymphoma: case report and review of literature

Intravascular large B‐cell lymphoma (IVLBCL) remains a diagnostic challenge, because of non‐specific findings on clinical, laboratory, and imaging studies. We present a case in which 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET)/computed tomography was particularly useful to suspect the diagnosis, to detect unexpected locations, to guide contributive biopsy, and to assess the response to treatment. In case of initial negative results, FDG‐PET should be repeated in the course of clinical evolution. In the presence of neurological or hormonal symptoms without brain magnetic resonance imaging abnormality, FDG‐PET brain slices could depict additional pituitary and/or brain hypermetabolisms. We discuss the potential interests of FDG‐PET in IVLBCL by a literature review. Copyright

Autoimmune hemolytic anemia after nivolumab treatment in Hodgkin lymphoma responsive to immunosuppressive treatment. A case report

The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune‐like syndromes.

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.

The Relevance of Testing the Efficacy of Anti-Angiogenesis Treatments on Cells Derived from Primary Tumors: A New Method for the Personalized Treatment of Renal Cell Carcinoma

Despite the numerous available drugs, the most appropriate treatments for patients affected by common or rare renal cell carcinomas (RCC), like those associated with the Xp11.2 translocation/transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) gene fusion (TFE3 RCC), are not clearly defined. We aimed to make a parallel between the sensitivity to targeted therapies on living patients and on cells derived from the initial tumor. Three patients diagnosed with a metastatic RCC (one clear cell RCC [ccRCC], two TFE3 RCC) were treated with anti-angiogenesis drugs. The concentrations of the different drugs giving 50% inhibition of cell proliferation (IC50) were determined with the Thiazolyl Blue Tetrazolium Bromide (MTT) assay on cells from the primary tumors and a reference sensitive RCC cell line (786-O). We considered the cells to be sensitive if the IC50 was lower or equal to that in 786-O cells, and insensitive if the IC50 was higher to that in 786-O cells (IC 50 of 6±1 µM for sunitinib, 10±1 µM for everolimus and 6±1 µM for sorafenib). Based on this standard, the response in patients and in cells was equivalent. The efficacy of anti-angiogenesis therapies was also tested in cells obtained from five patients with non-metastatic ccRCC, and untreated as recommended by clinical practice in order to determine the best treatment in case of progression toward a metastatic grade. In vitro experiments may represent a method for evaluating the best first-line treatment for personalized management of ccRCC during the period following surgery.

BRENTUXIMAB-VEDOTIN AND BENDAMUSTINE IS A FEASIBLE AND EFFECTIVE DRUG COMBINATION AS FIRST-LINE TREATMENT OF HODGKIN LYMPHOMA IN THE ELDERLY (HALO TRIAL).

11.97, P = .012; HR = 5.54, CI95% 2.13‐14.37, P<.001; HR = 6.75, CI95% 2.07‐21.96, P = .001). Long termOS in R/R HL is 59%; GFRS in these patients is 34% at 1 year and 26% at 5 years. Most patients allografted for R/R HL eventually survive without moderate to severe cGVHD and cGVHD‐free OS is 51%. Therefore, this survival outcome should be the benchmark to compare results of novel drugs such as checkpoint inhibitors in R/R HL patients.

Pharmacokinetics of trabectedin on hemodialysis: an application for the management of cancer patients with end-stage renal disease

PurposeThe pharmacokinetics of trabectedin has never been reported in patients with impaired renal function or in patients on hemodialysis.MethodsWe examined trabectedin PK in a patient on hemodialysis, starting trabectedin therapy at a standard dose for recurrence of a retroperitoneal myxoid liposarcoma that had occurred under immunosuppressive drugs for kidney transplant.ResultsAs compared with a population with normal renal function, the study patient presented a higher Cmax and AUC, with lower clearance, terminal half-life, and volume of distribution. The low dialysis clearance, accounting for a minor part of the total body clearance and the absence of detectable trabectedin in the dialysate samples, suggests that hemodialysis does not efficiently clear trabectedin. Trabectedin tolerance was good.ConclusionsThis case reports for the first time the feasibility of trabectedin therapy in a hemodialyzed patient. Given the rising incidence of cancer in patients with end-stage renal disease, it is crucial to provide data that improve the management of anticancer drugs in dialyzed patients.