Front-line fludarabine-cyclophosphamide-rituximab (FCR) in 110 patients with chronic lymphocytic leukaemia (CLL): real-life experience with long-term outcomes, toxicities and responses to second-line therapies.

Fludarabine-cyclophosphamide-rituximab (FCR) has been the gold standard front-line treatment for fit CLL patients until novel agent's introduction. Decision between either time-limited FCR or "endless" Bruton's tyrosine kinase inhibitor (BTKi) therapy may be difficult in fit IGHV-mutated-non-TP53 cases. We describe the outcomes after front-line FCR in 110 CLL patients from 5 centres in Catalonia, Spain, over a period of more than 10 years. ORR was 96.3% and CR 74.5%. Median second-treatment free survival (TFS1) was 6.2 years and median OS was 10.8 years. 50 (45.5%) patients required a subsequent therapy. Median third-treatment free survival was better for BTKi than for chemotherapy ± antiCD20 strategies (not reached vs 3.1 years, p = 0.003). Only 50 (45.5%) patients completed 6 cycles of FCR, and the main reason for discontinuation was cytopenia 29 (26.4%). 15 (13.6%) patients developed a second cancer, and 5 (4.5%) patients experienced a Richter's transformation (RT). At the end of follow-up, 50 (45.5%) patients remained in CR. Response rates, TFS1, OS, RT, and second cancers did not differ between patients treated with 6 vs 4 cycles of FCR. In conclusion, front-line FCR treatment leads to very long CR in almost half of patients, and BTKi yields excellent outcomes in relapsed patients.

Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which is the only one defined by a cytogenetic abnormality that makes these patients candidates to be treated with lenalidomide. During the last decade, single cell (SC) analysis has emerged as a powerful tool to decipher clonal architecture and to further understand cancer and other diseases at higher resolution level compared to bulk sequencing techniques. In this study, a SC approach was used to analyze intratumoral heterogeneity in four patients with MDS del(5q). Single CD34+CD117+CD45+CD19- bone marrow hematopoietic stem progenitor cells were isolated using the C1 system (Fluidigm) from diagnosis or before receiving any treatment and from available follow-up samples. Selected somatic alterations were further analyzed in SC by high-throughput qPCR (Biomark HD, Fluidigm) using specific TaqMan assays. A median of 175 cells per sample were analyzed. Inferred clonal architectures were relatively simple and either linear or branching. Similar to previous studies based on bulk sequencing to infer clonal architecture, we were able to observe that an ancestral event in one patient can appear as a secondary hit in another one, thus reflecting the high intratumoral heterogeneity in MDS del(5q) and the importance of patient-specific molecular characterization.

Acute liver failure as the first manifestation of very late relapsing of Hodgkin's disease.

Hodgkin's disease is, in general, a lymph node-based disease. It usually starts in an area within the lymphatic system and spreads, in an orderly manner, along the lymphatic chain to contiguous lymph node areas. There have been sporadic case reports of acute liver failure caused by hematological malignancies. Generally, liver failure is a feature of stage IV end-stage disease, when it occurs in lymphoma. Thus, hepatic involvement usually occurs late in the course of Hodgkin's disease or with advanced-stage disease, and primary presentation in the liver with acute liver failure is extremely rare. In most cases, the diagnosis was made at autopsy. We describe a patient with Hodgkin's disease presenting with acute liver failure. This is a very unusual Hodgkin's disease form of presentation, because the acute liver failure was the presenting feature of the disease. Furthermore, the lymphoma occurred as a very late relapse, twenty years after the first diagnosis. To the best of our knowledge, such a case has not been described to date.

Stroke in a multiple myeloma patient treated with thalidomide.

The antiangiogenic and immunomodulatory properties of thalidomide have led to its use and evaluation in refractory or relapsed multiple myeloma (MM). However, thalidomide use is associated with several side effects, although deep vein thrombosis and peripheral neuropathy are the most serious. The incidence of thrombosis after treatment with thalidomide ranges from 2% to 23%, but is higher among patients who also receive chemotherapy. Thromboembolic episodes are usually venous and may cause pulmonary embolism or even myocardial infarction and cerebral venous thrombosis. Arterial occlusion is rare, and the association between arterial thrombotic events and thalidomide is infrequent with only a few patients reported who developed arterial strokes on thalidomide. We describe a case of nonfatal thrombotic stroke occurring in a patient with relapsed MM treated with thalidomide.

Infección diseminada por citomegalovirus en una paciente diagnosticada de linfoma T periférico (variante Lennert) / Disseminated cytomegalovirus infection in a patient with peripheral T cell unspecified (variant-Lennert) non-Hodgking lymphoma

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Mixed chimerism is frequent after allogeneic peripheral blood stem cell transplantation with positive CD34 selection, and is not reverted by low doses of donor T-cells add-back.

UNLABELLED: The incidence of full donor chimerism (full DC) after CD34+ -selected peripheral blood stem cell transplantation (CD34+ -PBSCT) is controversial. Whereas the initial reports suggested a high incidence of full DC (hypothetically because of the high number of CD34+ cells infused) more recent works describe a high incidence of mixed lymphoid chimerism. There are no data concerning the ability of low-dose donor T-lymphocyte add-back on conversion to full DC. METHODS: We prospectively monitored the chimerism status of 25 patients undergoing CD34+ -PBSCT and the effect on chimerism of delayed low doses of donor T-cell add-back (TCAB). One, two or three doses of TCAB were administered on days +28 (2 x 10(5) CD3+/kg), +60 (2 x 10(5) CD3+/kg) and +90 (2 x 10(6) CD3+/kg), respectively, when on cyclosporine A prophylaxis. RESULTS: Incidence of full DC on day +20 was 56%. However, all but two patients progressed to MC. Fifteen patients were scheduled to TCAB. Six patients with initial MC did not convert to full DC after TCAB. Moreover, seven patients with full DC status progressed to mixed chimerism. CONCLUSIONS: Our results indicate that low doses of TCAB administered under cyclosporine A prophylaxis have no effect on the eradication of the recipient cells. We believe that a high dose of CD34+ cells in the grafts of CD34+ -PBSCT is not enough to achieve stable full DC unless a minimum number of CD3+ cells are infused, or more intensified transplant conditioning regimens are employed.