Liliana Calabrese

Clinical Activity of Rituximab in Gastric Marginal Zone Non-Hodgkin's Lymphoma Resistant to or Not Eligible for Anti–Helicobacter Pylori Therapy

PURPOSE Preliminary results using rituximab in extranodal marginal zone (MALT) non-Hodgkins lymphoma (NHL) patients seem to indicate a relevant clinical activity. Aim of the present study is to investigate the efficacy of conventional weekly treatment using rituximab in gastric MALT NHL patients resistant/refractory or not suitable for eradication treatment, and to evaluate the relevance of the t(11; 18)(q21; q21) translocation and its possible role as a predictive criteria of response. PATIENTS AND METHODS Twenty-seven patients presenting with gastric MALT NHL at any stage, relapsed/refractory to initial treatment or not suitable for eradication were treated with rituximab in a weekly conventional schedule and evaluated for response and relapse. Flourescence in situ hybridization (FISH) analysis for the presence of 18q21 translocation was performed in 21 patients and was evaluated with clinical outcome. RESULTS Among the 26 evaluated patients, 20 (77%) achieved an objective response. Twelve patients (46%) had a pathological and clinical complete remission, and eight (31%) had a partial response. With a median follow-up of 33 months, only two patients relapsed at 26 and 14 months, respectively. No correlation was founded between FISH analysis and response or relapse. CONCLUSION Our experience seems to confirm the clinical activity of rituximab in gastric MALT NHL patients resistant/refractory to antibiotics treatment or not presenting with clinical evidence of Helicobacter pylori infection. The t(11; 18)(q21; q21) translocation seems not to be a predictive marker to response or to subsequent relapse.

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

Treatment of acute leukaemia in adult Jehovahs 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 × 109)/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.

Early stage gastric diffuse large B-cell lymphomas: results of a randomised trial comparing chemotherapy alone versus chemotherapy + involved field radiotherapy

Here, we present the results of a randomised clinical trial carried out between 1998 and 2004, evaluating the possible role of radiotherapy (RT) as consolidation treatment after induction chemotherapy (CT) in diffuse large B-cell (DLBC) gastric lymphoma. Fifty-four patients were enrolled and all received anthracycline containing regimens as induction CT. Patients were evaluated after four to six cycles and those in complete remission (CR) were randomised to receive gastric involved field (IF) RT or two addition cycles of the same CT. Forty-five patients (83%) were randomised after the induction CT. Clinical results of patients allocated to the RT arm showed a significant reduction in incidence of local relapse versus patients who received CT alone. However, overall survival was not different between the two arms. Our results confirm that CT could be considered as first line therapy for newly diagnosed gastric DLBC lymphoma; IF RT delivered in those patients achieving CR after induction CT is able to prevent local relapse.

Rituximab and subcutaneous cladribine in chronic lymphocytic leukemia for newly diagnosed and relapsed patients.

The aim of this study was to investigate the efficacy of combined treatment with rituximab and subcutaneous cladribine in patients with newly diagnosed and relapsed chronic lymphocytic leukemia (CLL). Forty-three patients with active CLL or small lymphocytic lymphoma received rituximab 375 mg/m2 on day 1 and cladribine 0.1 mg/kg subcutaneously on days 2–6. The treatment was repeated every 4 weeks for a total of four cycles. Sixteen patients were pretreated. The overall response rate was 88% (50% complete remission and 38% partial remission). The median time to treatment failure was 37.9 months. Grade 4 neutropenia developed in 5% of patients. The data indicate that combination therapy with rituximab and cladribine is a valuable and safe treatment for patients with CLL.

ChlVPP/ABVVP, a first line ‘hybrid’ combination chemotherapy for advanced Hodgkin's lymphoma: a retrospective analysis

We retrospectively analysed toxicities and clinical results of 61 Hodgkins lymphoma patients treated with chlorambucil, vinblastine, procarbazine, doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a weekly alternate schedule. Of 61 patients, 33 were in stages III–IV, 21 in stage IIB and seven in stage IIA with bulky disease or extranodal presentation. ChlVPP/ABVVP was administered for 6–8 cycles. Involved field radiotherapy (IFRT) (30–35 Gy) was delivered to 31 patients with residual disease after chemotherapy or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete clinical or radiological remission after chemotherapy and IFRT. With a median follow‐up of 60 months, 5‐year overall survival, relapse‐ and event‐free survival were 78·8% (95% CI 68·2–91·1%), 81% (95% CI 70·6–92·2%) and 71·9% (95% CI 68·2–82·2%) respectively. Grades 3–4 neutropenia was the most relevant haematological toxicity and occurred in 82% of patients. Non‐haematological toxicities were mild and reversible. No toxic deaths were recorded. One patient developed secondary acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective nature of this study, no definitive conclusions could be drawn about the clinical activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone), MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), with a lower degree of haematological and non‐haematological toxicity. Long‐term results of the ongoing randomized trial, comparing ABVD versus high‐dose intensity weekly regimens will be useful to confirm our results.

Efficacy of 90Yttrium‐ibritumomab tiuxetan in relapsed/refractory extranodal marginal‐zone lymphoma

We evaluated clinical activity of 90Yttrium‐ibritumomab (90Y‐ibritumomab) tiuxetan in extranodal marginal‐zone lymphoma. From May 2004 to April 2011, 30 patients affected by relapsed/refractory marginal‐zone lymphoma—arisen at any extranodal site—received 90Y‐ibritumomab tiuxetan at the activity of 0.4 mCi/kg. Median age was 57 years. At time of treatment, 13 out of 30 patients had disseminated disease (stage III/IV). All patients had received a previous treatment with a maximum of 7. Overall response rate was 90%: 23 patients achieved a complete response (77%); partial response occurred in 4 patients (13%), stable disease in 2 patients (7%) and 1 progression (3%). With a median follow‐up of 5.3 years, median time to relapse was not reached; 2 patients relapsed after complete response; 18 out of 23 complete responses are still responders after >3 years, 12 of them after >5 years. 90Y‐ibritumomab tiuxetan seems to be active in patients with extranodal marginal‐zone lymphoma relapsed/refractory to conventional treatment including radiotherapy. These results suggest that radioimmunotherapy could represent a possible option for the treatment in this subset of patients. Copyright

Tissue Microarrays in Diffuse Large B-Cell Lymphomas Are They Really Able to Identify Distinct Prognostic Groups in Lymphomas of Both Nodal and Extranodal Origin?

Aims. Diffuse large B-cell lymphomas (DLBCL) can be divided into different subgroups (germinal center B-cell-like [GCB] and non-GCB) according to their gene expression profiles. Immunohistochemistry has been proposed as a surrogate for identifying these subgroups, but data about its efficacy in providing prognostic information are conflicting. Methods and results. This study retrospectively analyzed a series of 105 DLBCL, defined as GCB and non-GCB according to CD10, bcl-6, and MUM1 expression. All patients received a first-line anthracycline-based (CHOP-like) chemotherapy. A total of 50 patients (48%) were identified as GCB and 55 (52%) as non-GCB. The overall response rate was 89% (94/105), with 62 (59%) complete response. Disease progressions were equally distributed between the 2 subgroups and were not significantly different (P = .756) considering the primary site of involvement (nodal or extranodal). The median follow-up was 62 months (range 5-126 months). Overall survival at 5 years was not significantly different between the groups (P = .3468) and was 72.3% and 66.6% for GCB and non-GCB, respectively. Conclusion. The results do not support the prognostic value of GCB and non-GCB immunohistochemical categories in DLBCL of both nodal and extranodal origin. Furthermore, a limited number of antigens may be not sufficient to identify the same patterns defined by cDNA microarray. Prospective studies are warranted to address this issue.

Immunoreactivity for cyclin D1 is a reliable marker of gene aberration in plasma cell myeloma but does not specify patients prognosis.

2] Boren J, Cascante M, Marin S, et al. Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. J Biol Chem 2001;276:37747–53. 3] Barnes K, McIntosh E, Whetton AD, et al. Chronic myeloid leukaemia: an investigation into the role of Bcr-Abl-induced abnormalities in glucose transport regulation. Oncogene 2005;24:3257–67. 4] Breccia M, Muscaritoli M, Aversa Z, Mandelli F, Alimena G. Imatinib mesylate may improve fasting blood glucose in diabetic Ph+ chronic myelogenous leukemia patients responsive to treatment. J Clin Oncol 2005;22:4653–5. 5] Hagerkvist R, Sandler S, Mokhtari D, Welsh N. Amelioration of diabetes by imatinib mesylate (Gleevec): role of beta-cell NF-kappaB activation and anti-apoptotic preconditioning. FASEB J 2007;21:618–28. 6] Breccia M, Muscaritoli M, Gentilini F, Latagliata R, Carmosino I, Rossi Fanelli F, et al. Impaired fasting glucose level as metabolic side effect of nilotinib in non-diabetic chronic myeloid leukemia patients resistant to imatinib. Leuk Res 2007;31:1770–2. 7] Cheng H, Straub SG, Sharp GW. Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release. Am J Physiol Endocrinol Metab 2007;292:845–52.