Report on the 56th ASH Annual Meeting, San Francisco, 4-9 December 2014.

The 56th annual ASH (American Society of Haematology) meeting was held in San Francisco (CA). More than 3,000 abstracts were selected for presentation due to the huge amount of information from basic science to clinical experience. The future direction in haematoncology is targeted therapies for most diseases; for instance, anti-PD-1 and CAR-T cells in lymphoproliferative disorders and novel immunomodulatory agents active in the contest of bone marrow milieu in multiple myeloma. On the other hand, in aggressive haematological diseases (AML, ALL), clinical studies demonstrated the feasibility of a more intensive chemotherapy approach in older patients.

Effect on renal function of an iso-osmolar contrast agent in patients with monoclonal gammopathies.

OBJECTIVE: To assess the safety of the non-ionic iso-osmolar contrast agent iodixanol on renal function in patients with monoclonal gammopathies undergoing CT. METHODS: We explored the effect of iodixanol on renal function in 30 patients with monoclonal gammopathies and 20 oncological patients with a normal electrophoretic profile (control group). The parameters used to estimate renal function were: serum creatinine, eGFR (determined 24 h before and 48 h after the administration of iodixanol), and urinary excretion of Neutrophil Gelatinase-Associated Lipocalin (NGAL) determined 2 h and 24 h after. Serum creatinine was also determined 1 month after the administration of iodixanol. RESULTS: No significant increase in serum creatinine values were observed in the monoclonal gammopathies group and in 19/20 patients in the control group. Only 1 patient in the control group developed a transient contrast agent-induced nephropathy. We found no statistically significant difference between the two groups regarding the percentage variation from baseline values of serum creatinine, creatinine clearance, NGAL 2 h after, and eGFR. Whereas NGAL at 24 h showed a statistically significant increase in patients with Monoclonal gammopathies. CONCLUSION: The use of iodixanol appears to be safe in patients with monoclonal gammopathies and an eGFR≥ 60 ml/min/1.73 mq.

Lymphocytic toxicity in patients after peptide-receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC.

PURPOSE: Peptide-receptor radionuclide therapy (PRRT) with somatostatin analogs is an efficient new tool in patients with neuroendocrine tumors, with low risk of toxicity. Since lymphocytes express somatostatin receptors, the aim of this study was to evaluate lymphocytic toxicity after PRRT. METHODS: From May 2005 to May 2007, 16 patients affected by neuroendocrine tumors received PRRT with (90)Y-DOTATOC (9), (177)Lu-DOTATATE (5), or both (2). Absolute count, percentage of leukocytes and lymphocytes, and lymphoid subsets (B, T, and NK) were tested at baseline and until 90 days after treatment. RESULTS: A significant lymphoid toxicity (G2-3), mainly affecting B-cells, was observed. It was particularly evident after (90)Y-DOTATOC. Toxicity resulted in being transient and resolved completely at the end of the follow-up (90 days). CONCLUSION: Lymphocyte toxicity in PRRT is mainly due to the selective targeting on B-cells. The relative sparing of T-lymphocytes could explain the absence of clinical side-effects in these patients, such as increased risk of infections. These findings open interesting perspectives in the treatment of B-cell lymphoproliferative disorders.

Coagulation disorders in patients with cancer: nontunneled central venous catheter placement with US guidance--a single-institution retrospective analysis.

PURPOSE: To assess the feasibility and safety of ultrasonographic (US) guidance in the placement of nontunneled central venous catheters (CVCs) in patients with cancer who had altered coagulation profiles. MATERIALS AND METHODS: The study was approved by the institutional review board; informed consent was obtained. Medical charts of all patients with cancer who underwent nontunneled CVC placement at the European Institute of Oncology, Milan, from September 2001 to August 2008 were retrospectively reviewed. Patients were considered to have coagulation disorders or risk of bleeding when they had the following: prothrombin time more than 1.2 times normal or activated partial thromboplastin time more than 1.2 times normal and/or platelet count less than 150 x 10(9)/L. Patients with a prothrombin time and partial thromboplastin time more than 2.2 times normal and/or a platelet count less than 50,000/mm(3) were considered to be at high risk for bleeding. Two hundred thirty-nine nontunneled CVCs were placed with US guidance in 157 patients. RESULTS: One hundred twenty-two (51%) of 239 nontunneled CVCs were inserted in patients with cancer who had hemostasic disorders. Forty-five (37%) of 122 nontunneled CVCs were implanted in patients considered to be at high risk for bleeding. All catheters were successfully placed at the first needle pass with no major complications such as bleeding or pneumothorax. Two hundred thirty-three (97%) nontunneled CVCs were placed in the subclavian vein, and six (3%) were placed in the internal jugular vein. No patient underwent any correction for an abnormal coagulation profile. CONCLUSION: In patients with cancer who had coagulation disorders, nontunneled CVC placement with US guidance was feasible and safe and did not require correction of coagulation parameters.

Mammaglobin expression in leukapheresis products is a predictive marker of poor prognosis in women with high-risk breast cancer.

PURPOSE: The purpose of this study was to investigate the incidence and prognostic relevance of tumor cell detection in granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cell collections (PBPCCs) using cytokeratin (CK), maspin (MAS), and mammaglobin (MAM) genes as epithelial cell markers. The population on which the study was conducted was drawn from stage III breast cancer patients undergoing high-dose chemotherapy and autologous transplantation with PBPCCs. EXPERIMENTAL DESIGN: One hundred and ninety-four patients were enrolled in the study and analyzed for tumor cell detection on the basis of 481 PBPCCs gathered before administration of chemotherapy. CK, MAS, and MAM gene expressions were investigated by means of the reverse transcription nested polymerase chain reaction, and those samples expressing CK were further hybridized with a radiolabeled internal probe to reduce false-positive results. Sensitivity and specificity were assessed on 37 controls (12 cell lines, 12 healthy donors, and 13 nonepithelial malignancies). Each of the known prognostic variables (age, stage, lymph node status, receptor status, c-ErbB2 status, and Ki67 status) was then analyzed (both individually and together with CK, MAS, and MAM expression on PBPCCs) in relation to patient overall survival (OS) and relapse-free survival (RFS). RESULTS: After a 3-year follow-up, an estimated 83% (95% confidence interval, 77.1-88.8%) of the patients were alive and an estimated 67% (95% confidence interval, 60.1-74.6%) were free of relapse. One hundred and seventy-six of the 194 patients (91%) had contaminated PBPCCs evidenced by at least one positive sample for any of the markers evaluated. The PBPCC frequency of CK, MAS, and MAM positivity (+) was 71%, 36%, and 16%, respectively. MAM expression on PBPCC was associated with an increased risk of relapse (P = 0.003), whereas CK and MAS expressions were not associated with changes in either RFS or OS. CONCLUSIONS: MAM gene expression on leukapheresis products of high-risk breast cancer patients is an indicator of poor prognosis. The method of evaluation is simple and reproducible and provides new tools for evaluating the role played by tumor cells in apheresis products and their potential in causing metastasis.

Tailored therapy of adult acute leukaemia in Jehovah's Witnesses: unjustified reluctance to treat.

Treatment of acute leukaemia in adult Jehovah's Witnesses (JW) is challenging because of 'a priori' refusal of most physicians to apply diagnostic and therapeutic procedures to haematological abnormalities resembling acute leukaemia. Rejection of blood transfusions by individuals of this faith is usually blamed to justify this attitude, thus leading to severe personal, medical and psychological distress related to the lack of care. We therefore intended to verify whether a standard (tailored) chemotherapy, without the use of prophylactic blood product transfusions, could be applied during treatment of acute leukaemia under such circumstances. Eleven consecutive JW adult patients with acute leukaemia, all of whom had been denied care in other institutions, were treated at the European Institute of Oncology (EIO) in Milan, Italy. Five had acute lymphoblastic leukaemia (ALL) (one bcr/abl positive), six had acute myeloid leukaemia (AML) with immunophenotype and/or cytogenetic intermediate-high risk features, except one patient with acute promyelocytic leukaemia (APML). Standard induction chemotherapy [cytosine arabinoside (ARA-C) and daunorubicin (DNR) for AML, vincristine (VCR), DNR and prednisone (PDN) for ALL, all-trans retinoic acid (ATRA) and DNR for APML] with the antracycline dose of at least 30 mg/sqm were used. All patients experienced severe anaemia after induction chemotherapy despite erythropoietin. Median haemoglobin nadir for patients with ALL and AML was 4.5 g/dL (range 1.3-6.9) and 5.1 g/dL (range 2.6-6.8), respectively. Median platelet nadir counts for all patients was 14.5 x 10(9))/L (range 1-24). One patient died during induction probably due to haemorrhage. Four of five patients with ALL achieved a complete remission (CR) (including the bcr/abl case) while among patients with AML only the one with APML achieved CR. Three patients (APML = 1 and ALL = 2) are still alive and disease-free. This small series of adult patients with leukaemia illustrates difficulties in treating patients who are practising JW, yet nevertheless provides a significant argument against the prejudicial decision leading to evasion of treatment in these patients.