Systemic amyloidosis due to unknown multiple myeloma in small bowel pseudo-obstruction: case report

Amyloidosis is a pathologic diagnosis characterized by extracellular deposition of insoluble protein fibrils in various organs and tissues. There are two main forms of amyloidosis, primary amyloidosis, and secondary amyloidosis. Gastrointestinal involvement is common in both amyloidosis forms. We describe the case of a 78-year-old woman taken to the operating room for small bowel obstruction, found to have pseudo-obstruction and enteritis. Exploratory laparotomy revealed gastric mass and histological examen showed extensive amyloid deposition consistent with amyloidosis. Hematological evaluation revealed unknown multiple myeloma. This case report and literature data suggest to perform a hematological examination in patients with amyloidosis diagnosis to exclude a multiple myeloma or other plasma cell disorder

Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505

Prophylactic cranial irradiation in extensive disease small cell lung cancer : an endless debate

Extensive disease Small cell lung cancer (ED-SCLC) represents a very aggressive malignancy in which brain metastases (BM) are quite common. Clinical trials on prophylactic cranial irradiation (PCI) have showed a clear decrease in the risk of developing BM but conflicting results concerning a possible survival advantage. A landmark European Organisation for Research and Treatment of Cancer (EORTC) prospective trial, as well as multitude of retrospective series confirm survival benefit after PCI. Recently, a Japan Clinical Oncology Group (JCOG) study did not find such survival benefit, provided that non-irradiated patients are closely followed by MRI. Henceforth, the role of PCI in this population has been questioned, on the ground of the possible absence of survival benefit, leading to a gradual shift in oncology practice. We performed a review of the literature on the subject of PCI in ED-SCLC patients. We conclude that PCI could still play a crucial role in these patients, considering not only a possible survival benefit, but also alternative endpoints, such as improved local control, delay in the onset of symptomatic BM and lower toxicity of a prophylactic- rather than an eventual active-intent treatment. Individualized attitude should be discussed with patients, while addressing all arguments in favour and against PCI

Imatinib treatment inhibit IL-6, IL-8, NF-KB and AP-1 production and modulate intracellular calcium in CML patients

Imatinib (IM) is considered the gold standard for chronic myeloid leukemia (CML) treatment, although resistance is emerging as a significant problem. The proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) play an important role in cell proliferation, survival, and resistance to glucocorticoid-mediated cell death. Several transcription factors such as NF-KB and AP-1 are activated in response to physiopathological increases and modulation of intracellular calcium levels. Our previous study demonstrated that lymphocytes from CML patients showed dysregulated calcium homeostasis and oxidative stress. Alteration in ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation. In this study, we hypothesized that IL-6, IL-8, NF-kB, AP-1, and intracellular calcium may be used as selective and prognostic factors to address the follow-up in CML patients treated with imatinib. Our results demonstrated a significant down-regulation in IL-6 and IL-8 release as well as NF-kB and AP-1 activation in lymphomonocytes from Imatinib-treated patients, compared to samples from untreated patients. In parallel, IM treatment, in vivo and in vitro, were able to modulate the intracellular calcium concentration of peripheral blood mononuclear cells of CML patients by acting at the level of InsP(3) receptor in the endoplasmic reticulum and at the level of the purinergic receptors on plasma membrane. The results of this study show that measurements of NF-kB, AP-1, IL-6, IL-8, and intracellular calcium in CML patients treated with Imatinib may give important information to the hematologist on diagnostic criteria and are highly predictive in patients with newly diagnosed CML

Analysis of Frequency and Risk Factors for Developing Bisphosphonate Associated Osteonecrosis of the Jaw.

Although the evidence available associating bisphosphonates (BP) with osteonecrosis of the jaw (ONJ) is far from conclusive, the growing literature reports strongly suggest a strict relationship between them. The real frequency of this complication is unknown because of the recent observation of this condition, the bias related to retrospective studies and the wide-spread use of this supportive therapy. Aims of this research were to look for additional risk factors for developing ONJ and to determine the frequency of this event in the subgroup of patients affected by Multiple Myeloma (MM) treated with BP. We asked 49 GISL centers to participate in a retrospective multicenter study filling out a form containing several queries, including sex and age, anamnesis for smoke habit, anemia and thrombotic events, type and time of neoplasia diagnosis, treatment and neoplasia status, odonthoiatric anamnesis, type and duration of therapy with BP, microbial isolation in site of lesion, specific treatment for osteonecrosis, number of patients (pts) affected by MM treated with BP from 2002 to 2005. Fifteen centers decided to participate in the study and 12 had cases of osteonecrosis. ONJ was reported in 19 pts. Sixty % were females and the median age was 65 ys. Sixteen had MM, 1 breast cancer, 1 prostatic cancer, 1 osteoporosis steroid related. Median time from diagnosis of cancer was 54 months and median duration of treatment with BP was 34 months. Thirteen events manifested between 20 and 60 months. Of the 19 pts, 8 had received zolendronate, 2 pamidronate and 9 both drugs. None had radiotherapy on head and neck, while two received total body irradiation. In these two cases, ONJ was associated with necrosis of the pelvis. The 2 solid tumors were treated with ormonal therapy. All MM pts had received one or more line of treatment including, VAD, MP, steroids and thalidomide alone or in combination, as well as high dose melphalan, as part of autologous bone marrow transplant. ONJ involved the mandible in 14 pts, the maxilla in 3 and both in 2. Symptoms included local pain and discomfort. In 17 cases CT scan was the strumental procedure used to identifiy the lesion. In 14 pts biopsy was performed excluding localization of neoplasia in 11 cases. Microbiological evaluation of the lesion was positive in 11 pts, with 6 cases of Actynomices. In 12 patients ONJ was apparently spontaneous; in 7 occurred after dental procedures. Parodonthopaties were present in 10 pts. In 11 cases ONJ was complicated by fistula, exposed bone or abscess. BP were stopped in 17 pts. Antibiothic therapy was administered in 17 cases; 7 pts underwent hyperbaric oxygen therapy and 8 surgical debridement. Several pts improved but none were cured. Considering only the MM subgroup 16 cases of ONJ were identified among 888 pts treated with BP between 2002 and 2005, with a frequency of 1.8%. Utilizing the data collected by our retrospective study a fine statistical analysis is not applicable. However, in MM pts the frequency of steroid treatment, parodonthopaties and anemia was particularly high, respectively 100%, 56%, and 56%, supporting the idea that these are additional risk factors for developing ONJ

Comparison of Dasatinib, Nilotinib, and Imatinib in the Treatment of Chronic Myeloid Leukemia

To overcome the drug resistance phenomenon induced by Imatibib (IM), in clinical practice, are often used second generation of tyrosine kinase inhibitors as Nilotinib (NIL); a such potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS), a inhibitor of BCR/ABL kinase, and inhibitor SrC family kinase. In this study we evaluated the in vivo effect of DAS, NIL, and IM on intracellular calcium concentration, oxidative stress, and apoptosis in peripheral blood leukocytes of 45 newly diagnosed patients with chronic myeloid leukaemia (CML-PBM). Our data demonstrated that treatment with DAS and NIL showed an higher modulating potential than IM on intracellular calcium concentration by inhibiting the thapsigargin, a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, and Lithium (Li) an inositol 1,4,5-triphosphate (InsP3) receptor inhibitor activities. Moreover our data demonstrated that NIL and DAS have significantly increased apoptosis more than IM by involving both intracellular calcium signaling as well as oxidative stress. The acquisition of the oxidative stress and calcium channels receptors values data could help the hematologist to modulate and improve the treatment of chronic myeloid leukaemia (CML) pathology

Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: Results of a retrospective, observational GIMEMA study

In patients with immune thrombocytopenia (ITP) refractory to corticosteroids and intravenous immunoglobulins (IVIG), splenectomy may result at higher risk of peri-operative complications and, for this reason, potentially contraindicated. The thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag have shown high therapeutic activity in primary ITP, but data of efficacy and safety regarding their use in preparation for splenectomy are missing. Thirty-one adult patients, median age 50 years, with corticosteroids and/or IVIG refractory persistent and chronic ITP who were treated with TPO-RAs (romiplostim= 24; eltrombopag= 7) with the aim to increase platelet count and allow a safer execution of splenectomy were retrospectively evaluated. Twenty-four patients (77%) responded to the use of TPO-RAs with a median platelet count that increased from 11 7 109/L before starting TPO-RAs to 114 7 109/L pre-splenectomy, but a concomitant treatment with corticosteroids and/or IVIG was required in 19 patients. Twenty-nine patients underwent splenectomy while two patients who responded to TPO-RAs subsequently refused surgery. Post-splenectomy complications were characterized by two Grade 3 thrombotic events (1 portal vein thrombosis in the patient with previous history of HCV hepatitis and 1 pulmonary embolism), with a platelet count at the time of thrombosis of 260 and 167 7 109/L, respectively and one Grade 3 infectious event. TPO-RAs may represent a therapeutic option to improve platelet count and reduce the risk of peri-operative complications in ITP candidates to splenectomy. An increased risk of post-splenectomy thromboembolic events cannot be ruled out and thromboprophylaxis with low-molecular weight heparin is generally recommended. \ua9 2016 Wiley Periodicals, Inc

Combination of bendamustine and rituximab as front-line therapy for patients with chronic lymphocytic leukaemia: Multicenter, retrospective clinical practice experience with 279 cases outside of controlled clinical trials

Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine-rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008-2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43-86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remission rate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS ≥7, immunoglobulin heavy-chain variable-region (IGHV) unmutated status, del17p and BR dose intensity <80% were independently associated with shorter PFS. Grade III or IV neutropenia, thrombocytopenia, and anaemia were observed in 25.9%, 15.4%, and 15.1% of patients, respectively. Twenty-four patients (8.6%) had severe infections. BR is also an effective and safe regimen for untreated CLL patients, outside of controlled clinical trials