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Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph‐chromosome and the BCR‐ABL tyrosine‐kinase (TK). Target‐therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second‐generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin−Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in‐vivo activity and timecourse of first‐line Nilotinib therapy on BM CD34+/lin−Ph+ cells clearance. Eighty‐seven CP‐CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin− cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per‐Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin− cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK‐STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed. [ABSTRACT FROM AUTHOR]

Lenalidomide is effective against relapsed chronic lymphocytic leukemia ( CLL). We report the first case of long-term molecular remission with continuous lenalidomide treatment in a young patient with CLL relapsed to multiple treatments. Minimal residual disease was assessed by nested polymerase chain reaction on bone marrow samples with patient-specific primers. A 20-yr-old patient with standard-risk CLL was treated with lenalidomide after multiple relapses and achieved a 4 yr long complete molecular response with minimal toxicities. Published biologic data support that lenalidomide induces an immune-mediated control of CLL, and our case suggests that long-term treatment with lenalidomide is effective at a molecular level in patients with relapsed CLL. [ABSTRACT FROM AUTHOR]

Objectives The efficacy of a novel vaccine against influenza virus A ( H1 N1) in patients with hematologic malignancies is largely unknown. Methods We prospectively evaluated the humoral and cellular immune responses after one injection of monovalent adjuvanted 2009 H1 N1 vaccine in 47 adults with hematologic malignancies and 77 controls by hemagglutination-inhibition assay and flow-cytometry analysis on day 0, 28, 50, and 90. Results On day 28 postvaccination, patients had lower seroprotection (95.2% vs. 75.2%, P < 0.01) and seroconversion (88.7% vs. 51.1%, P < 0.01) rates, as well as geometric mean titer ( GMT; 256 vs. 134, P < 0.05), relative to controls. Response to vaccination varied according to the evaluated time point and the patient status: Patients not receiving chemotherapy had seroprotection and GMTs similar to controls in all time points, while patients receiving chemotherapy or allogeneic hematopoietic stem cell transplant ( HSCT) had lower seroprotection and seroconversion levels than controls on day 28 and 50. EMEA cutoffs for efficacy were reached from day 28 by patients in follow-up or under treatment and only from day 90 by those with HSCT, especially if still under immunosuppressants. Patients treated with immunomodulatory drugs had higher antibody responses in terms of seroprotection and GMTs. T- and NK cell-mediated responses mounted from day 50 and did not differ between patients and controls. Conclusions According to EMEA recommendation, H1 N1 vaccination strategy was effective at protecting most of the hematologic patients, but needed to be improved in those more immunocompromised. [ABSTRACT FROM AUTHOR]