Antonello Sica

Increased hepatitis C viral load and reactivation of liver disease in HCV RNA-positive patients with onco-haematological disease undergoing chemotherapy

AIMS To evaluate changes in Hepatitis C Virus (HCV) RNA both in plasma and Peripheral Blood Mononuclear Cells (PBMC) in onco-haematological patients. PATIENTS AND METHODS 8 consecutive anti-HCV/HCV RNA-positive patients with onco-haematological diseases (5 with B-cell Non-Hodgkin Lymphoma and 3 with chronic lymphocytic leukaemia) were observed during chemotherapy and after its discontinuation. All were naïve to chemotherapy. HCV RNA was sought by Real Time Polymerase Chain Reaction in Light Cycler 1.5 in plasma and PBMC samples collected before, during and after chemotherapy. RESULTS An increase in HCV RNA of at least 1.5 log IU/mL in plasma and 1.1 log IU/ml in PBMC was observed in all 7 patients undergoing Rituximab-based chemotherapy; these patients showed a hepatic flare after discontinuation, life-threatening in one with cirrhosis. Also the 8th patient had cirrhosis, but was treated with Rituximab-sparing chemotherapy and did not show any increase in HCV RNA or a hepatic flare. CONCLUSION Rituximab-based chemotherapy favours an increase in HCV RNA in onco-haematological patients; this is followed by a hepatic flare, possibly immune-mediated and life threatening in cirrhotic patients.

Silent celiac disease in chronic hepatitis C - Impact of interferon treatment on the disease onset and clinical outcome

Goals: To assess the impact of interferon treatment on celiac disease onset in hepatitis C patients and to clarify its clinical relevance and outcome. Background: Hepatitis C is associated with autoimmunity, which can be exacerbated by interferon treatment. Cases of celiac disease activation during interferon treatment have been reported. Study: Retrospective evaluation of 534 hepatitis C patients with or without symptoms compatible with celiac disease onset during interferon treatment and 225 controls. Anti-transglutaminase antibodies were assayed. HLA-DQA1 and -B1 loci were typed. Upper gastrointestinal endoscopy was applied to confirm the diagnosis in antibody-positive patients. Results: Anti-transglutaminase antibodies were detected before treatment in 1.3% of hepatitis C patients and in 0.4% of controls (not significant). Eighty-six percent of patients with anti-transglutaminase antibodies showed activation of celiac disease while on interferon. Symptoms ranged from mild to severe, and interferon had to be discontinued in 2 of 7 (29%) patients. Symptoms disappeared in 6 of 7 patients after interferon withdrawal. Onset of symptoms compatible with celiac disease during interferon therapy was significantly associated with the presence of anti-transglutaminase antibodies (OR 53). Conclusions: In hepatitis C patients, the activation of silent celiac disease during interferon treatment is almost universal and should be suspected, but it uncommonly requires interferon treatment discontinuation. Symptoms subside after interferon withdrawal.

Is it possible to discontinue imatinib mesylate therapy in Chronic Myeloid Leukemia patients with undetectable BCR/ABL? A case report and a review of the literature.

Imatinib mesylate (IM) therapy leads to a complete cytogenetic response (CCyR) in 75-90% of Chronic Myeloid Leukemia (CML) patients in chronic phase, but only a small percentage of patients achieve complete molecular response (CMR). Very little is known about IM discontinuation. We report the case of a 20-years-old male patient in chronic phase CML who maintained undetectable BCR/ABL mRNA levels, despite IM discontinuation over a period of 15 months after achieving CMR. Our patient reached CCyR and CMR after 3 and 6 months of IM treatment, respectively. We also reviewed the published literature concerning cases of IM discontinuation.

Serum double monoclonal components and hematological malignancies: Only a casual association? Review of 34 cases

A double monoclonal component (MC) detected in the serum and/or urine represents a very rare occurrence (2-6% of monoclonal gammopathies). In this study, we report 34 patients with double serum MCs, focusing on the associated diseases. The diagnosis was made using high-resolution serum protein electrophoresis and immunofixation. Of the 1214 patients with monoclonal gammopathies, 49 had a double MC but only 34 (2.8%) were included in our study. A double MC was associated with hematological malignancies in 20/34 cases. Based on our experience, a double MC is more often associated with other diseases, especially an oncohematological one.

Clinical significance of serum triple monoclonal components: a report of 6 cases and a review of the literature.

A serum multiple monoclonal component (MC) is very rare. We here report 6 patients with 3 MCs. The triple MC was detected in all of them by immunofixation. 2/6 patients did not present hematological or oncological associated disease, while in the remaining 4, Waldenström macroglobulinaemia (2 cases), Polycythemia Vera and non-Hodgkin lymphoma were diagnosed. Of the 49 global patients reported in the literature (6+43), 64.6% had a lymphoproliferative disorder and only in 3 cases there was no associated disease. Therefore, the detection of such laboratory evidence should propel physicians to a deeper investigation.

Bilateral Lacrimal Gland Involvement With Mantle Cell Lymphoma

A 73-year-old woman presented with a rapidly growing bilateral orbital swelling, causing diplopia and epiphora. During physical examination, there were exophthalmos and orbital edema, both more prominent in the right eye (Figures 1A and 1B). The conjunctiva of both eyes was swollen. The lesions extended to the right iris and partially covered the left one. Computed tomography revealed, in both eyes, a mass (right eye: 2.7 cm 3 2.14 cm; left eye: 1.88 cm 3 1 cm) involving the lacrimal gland and adjacent to the superior rectus and lateral rectus muscles. Histological and immunohistochemical analyses showed a population of small atypical lymphocytes, with slightly irregular indented nuclei and moderately dispersed chromatin. Malignant cells were CD19+, CD20+, CD5+, CD232, CD102, and hyperexpression of cyclin D1 was detected. Cytogenetic analysis demonstrated the presence of a complex karyotype: t(11; 14)(q13; q32), t(7; 10)(q21; p12), dup (11)(q25, q13), and 217. The final diagnosis was mantle cell lymphoma (MCL), stage IV-A. The patient underwent 6 cycles of R-GIFOX (Rituximab-Gemcitabine, Ifosfamide, Oxaliplatin) achieving a complete response. Unfortunately, 18 months later, her disease relapsed (although at a different site), and she died 29 months after the initial diagnosis. Ocular adnexal lymphoma (OAL) accounts for approximately 1% to 2% of all non–Hodkgin’s lymphomas (NHL). OAL comprises both primary extranodal NHL and secondary involvement in systemic lymphomas. Although mucosa-associated lymphoid tissue represents the most common histology, MCL is observed in only very small percentages. MCL represents between 2% to 10% of all NHLs, and it has often an aggressive clinical behavior. The chromosomal translocation t(11; 14)(q13, q32), that juxtaposes the cyclin D1 and the immunoglobulin heavy chain genes, is detected in almost all cases, and it represents the molecular hallmark of MCL. The aim of treatment for younger patients still remains a long-lasting complete remission. In elderly patients treatment still represents a challenge. For fit elderly patients, long progression-free survival and molecular remissions are possible, whereas for the frail patients, the treatment should aim at reducing symptoms and maintaining quality of life (3).

Secondary Extramedullary Plasmacytoma of the Duodenum:An Unusual Endoscopic Presentation

We describe an unusual case (a 79-year-old woman) of secondary extramedullary plasmacytoma (EMP) involving the duodenum. While all the previously reported cases of duodenal involvement by EMP (namely 20 cases) were characterized by the presence of ulcerative masses or ischemic necrotic lesions, in our case EMP led to the unusual finding of several non-polypoid lesions with a depressed central area. The final diagnosis was multiple myeloma IgA lambda, stage II A, with secondary duodenal EMP. To our knowledge this is the first report showing duodenal involvement by EMP with the aspect of multiple non-polypoid lesions.