Interferon Alpha Has a Strong Anti-tumor Effect in Philadelphia-negative Myeloproliferative Neoplasms.

BACKGROUND: Despite the important progress in the research of myeloproliferative neoplasms (MPN), treatment options are still limited. Currently, a cytoreductive approach is the backbone treatment, with hydroxyurea (HU) being the most important agent. However, this drug is not always well-tolerated and has been questionably linked to a potential leukemogenic effect. A valid alternative is interferon alfa (IFN-α), but it is reserved for selected patients owing to the more frequent side effects and the lack of final results from the studies directly comparing IFN-α with HU, which is why we provided the results of the so far largest real-life analysis. PATIENTS AND METHODS: From 2000 to 2016, 63 patients with Philadelphia-negative MPN prospectively received either HU or IFN-α. RESULTS: During a median follow-up period of 121 months (range, 88-168 months), 97% of the patients treated with IFN-α achieved a hematologic response (60% complete, 37% partial) compared with 78% in the HU group (56% complete, 20% partial; P < .01). Molecular responses were limited to patients treated with IFN-α. IFN-α was well-tolerated with no secondary malignancy, whereas HU was associated with more toxic events and cases of leukemic transformation. A significantly longer progression-free survival (5.0 vs. 3.1 years; P < .001) and overall survival (7.8 vs. 5.8 years; P = .006) were observed in the IFN-α group compared with the HU cohort. CONCLUSION: Our data support IFN-α as a more valid therapeutic option owing to its more profound hematologic responses, durable molecular remissions, long-term disease control, and reduced risk of leukemic transformation with a favorable toxicity profile.

90Y-Ibritumomab-Tiuxetan Consolidation Therapy for Advanced-Stage Mantle Cell Lymphoma After First-Line Autologous Stem Cell Transplantation: Is It Time for a Step Forward?

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive lymphoma with a dismal prognosis because of numerous relapses. Because the most promising results have been obtained with immunochemotherapy followed by autologous cell stem transplantation (ASCT), we evaluated the efficacy of yttrium-90 ibritumomab ((90)Y-IT) consolidation after such an intensive treatment. PATIENTS AND METHODS: We retrospectively assessed 57 patients affected by intermediate or high-risk MCL in complete remission (CR) or partial remission (PR) after 3 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisolone) plus 3 cycles of R-DHAP (dexamethasone, cytarabine [Ara-C], cisplatin [platinum]) followed by ASCT and additional consolidation treatment with (90)Y-IT in 28 cases. All patients underwent 2 years of rituximab maintenance. RESULTS: After ASCT, 94% achieved CR and 4% achieved PR. The median follow-up was 6.2 years (range, 1.8-9.7 years). Treatment intensification was well tolerated and led to a significantly longer response duration in comparison to standard treatment. In contrast to the historical cohort, the addition of (90)Y-IT seems to overcome important risk factors such as Mantle Cell Lymphoma International Prognostic Index (MIPI) score and bone marrow infiltration. CONCLUSION: In the present retrospective analysis, immunochemotherapy followed by ASCT resulted in a very high response rate, and subsequent (90)Y-IT consolidation significantly reduced the number of relapses and increased survival, suggesting that (90)Y-IT consolidation might be a valid option in first-line treatment. However, a prospective confirmatory trial is warranted.

Extranodal diffuse large B-cell lymphoma with monoclonal gammopathy: an aggressive and primary refractory disease responding to an immunomodulatory agent.

BACKGROUND: Although the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) has been improved by the addition of rituximab to standard chemotherapy, almost one-third fails or relapses after first line treatment. The presence of monoclonal gammopathy (MG) is a known adverse prognostic factor for DLBCL. Because this subset of patients does not benefit from R-CHOP, new therapeutic options are required. Herein, we report the first case of extranodal DBCL of the lung with a concomitant MG who achieved a long lasting complete remission with lenalidomide. CASE PRESENTATION: The 73-year-old male patient presented with lateral cervical lymphadenopathy, B symptoms, lactate dehydrogenase and beta2-microglobulin elevation. Computed tomography (CT) showed mediastinal lymphadenopathy and bilateral lung involvement. Biopsy of both disease locations revealed the presence of DLBCL. Successive bone marrow trephine biopsy proved the presence of concordant DLBCL involvement. At the time of diagnosis, a MG was present as well. The patient did not respond to the standard treatments, and subsequently underwent lenalidomide 25 mg/m(2) days 1-21 q28 plus dexamethasone 40 mg days 1-4, 9-12 e 17-20. This therapeutic regimen was efficacious and safe as salvage therapy in extranodal DBCL with a MG. Furthermore, we observed a close association between DLBCL response to therapy and MG levels, suggesting that the amount of M-protein might be a surrogate marker of disease response. CONCLUSION: Although DLBCL associated with MG does not respond properly to the standard treatments, it is highly sensitive to lenalidomide, which is why we endorse its role as treatment of choice in this subset of patients. In addition, MG levels appear to correlate with tumor burden, suggesting that it might be a useful marker of disease response. Prospective trials to validate these observations are warranted.

90Y-Ibritumomab Tiuxetan consolidation after autologous stem cell transplantation improves survival of patients with intermediate-/high-risk diffuse large B-cell lymphoma not responding adequately to first-line treatment.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity whose prognosis for high-risk patients is poor. Aggressive salvage treatments to improve patient outcome have been unsatisfactory. Therefore, we evaluated the efficacy of yttrium-90-ibritumomab tiuxetan (Zevalin®; (90)Y-IT) consolidation after early salvage chemotherapy with autologous stem cell transplantation. Thirty-seven patients with intermediate-high risk DLBCL not in complete remission (CR) after three cycles of rituximab, cyclophosphomide, doxorubicin, vincristine and prednisone (R-CHOP) were assessed retrospectively. After early salvage treatment, 70% achieved CR and 30% partial remission. Twenty patients underwent additional consolidation with (90)Y-IT. During the 3-year follow-up, 50% in the (90)Y-IT-treated group experienced relapse compared to 82.3% in the other cohort (p=0.002). Progression- and disease-free survival were significantly longer in the (90)Y-IT group. However, probably due to the relatively short follow-up period, no difference in overall survival was observed. (90)Y-IT consolidation after early salvage chemotherapy improves treatment responses and reduces the percentage of relapses without significant additional toxicities.

Primary diffuse large B-cell lymphoma of the bone: bendamustine and rituximab are able to overcome resistant disease.

Primary bone lymphoma (PBL) is a rare disease for which specific therapeutic guidelines have not yet been established. Due to common appearance in the elderly and recurring relapses, new treatments are required. We report the case of multiple relapsed aggressive PBL effectively treated using Bendamustine and Rituximab. A 78-year-old male patient presented with a painful mass in the left arm. Computed tomography (CT) showed a pathological tissue in the humerus diaphysis infiltrating the muscle, confirmed by positron emission tomography (PET) scan. Indeed, PET excluded pathological local lymph node involvement. Biopsy of the humerus revealed the presence of diffuse large B cell lymphoma. Recommended treatments for PBL were used, but relapses after an initial complete response occurred. Following the positive experience of Vacirca et al. the patient underwent Bendamustin 90 mg/mq gg1-2 q28 plus Rituximab 375 mg/mq q28 (BR). Herein we report the first experience of BR combination in PBL and it proved to be an efficacious and safe salvage therapy in relapsed/refractory PBL.

Necrotizing fasciitis as a rare complication of osteonecrosis of the jaw in a patient with multiple myeloma treated with lenalidomide: case report and review of the literature.

Bisphosphonates (BPs), potent inhibitors of osteoclast-mediated bone resorption, play a major role in the management of patients with multiple myeloma (MM). However, in the case of dental infections, they can lead to bisphosphonate related osteonecrosis of the jaw (BRONJ). This process can be worsened by concomitant antineoplastic therapy. Herein, we present a case of a life-threatening necrotizing fasciitis (NF) as a rare and severe complication of BRONJ after three cycles of lenalidomide and dexamethasone in an MM patient treated with corticosteroid therapy and Ibandronate for 5 years. The patient presented swelling on the right part of the neck, difficulty in swallowing and acute pain, so a magnetic resonance of the head and neck region was performed. It revealed the presence of an NF with a massive extension. Due to the large necrotic area and a rapid progression of the infection, the necrotic tissue had to be removed surgically. Furthermore, a specific antimicrobial treatment as well as 12 sessions of hyperbaric oxygen therapy were needed to cure the patient. Herein, we highlight the potential serious adverse events associated with the use of bisphosphonates and antiangiogenetic drugs in patients with MM. Future studies are needed to evaluate the potential synergistic effects of BPs, corticosteroids and antiangiogenetic drugs.

Response to dasatinib in a patient with SQCC of the lung harboring a discoid-receptor-2 and synchronous chronic myelogenous leukemia.

We report a patient with squamous cell carcinoma (SQCC) of the lung and a discoid-receptor-2 (DDR2) kinase domain mutation that responded to dasatinib treatment. Our case report is consistent with previous publications suggesting that DDR2 mutation may confer sensitivity to dasatinib.

Fatal Hepatocellular Carcinoma in a Patient with Occult Hepatitis B Virus Infection following the Administration of R-CHOP for Diffuse Large B-Cell Lymphoma.

Occult hepatitis B (OBI) is caused by a persistent low-level replication of HBV. Like overt HBV infection, OBI can be associated with the integration of HBV sequences into the host genome and has a substantial clinical relevance for patients who are severely immunosuppressed for long durations. We present the case of a patient with a diffuse large B-cell non-Hodgkin lymphoma and OBI who developed a hepatocellular carcinoma with a fulminant clinical course following the administration of rituximab plus CHOP.

Secondary Leukemia in a non-Hodgkin's Lymphoma Patient Presenting as Myeloid Sarcoma of the Breast.

As defined by the World Health Organization classification of tumors of hematopoietic and lymphoid tissue, myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells that can arise before, concurrent with, or following acute myeloid leukaemia. We describe a case of secondary leukemia presenting itself as MS of the breast in a patient previously treated for a non-Hodgkin's Lymphoma.

Myelodysplastic syndrome appearing during imatinib mesylate therapy in a patient with GIST.

The introduction of imatinib has been a major advance in the treatment of gastrointestinal stromal tumor (GIST). However, despite its remarkable efficacy and toxicity profile little is known about the potential for long-term toxicity. This may be an important issue because some patients (pts) with chronic myelogenous leukemia (CML) develop, during imatinib treatment, chromosomal abnormalities in philadelphia chromosome (Ph) negative cells with evolution to myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), furthermore a nonrandom association between GIST and myeloid leukemia has been recently reported. We report here a case of refractory cytopenia with mutilineage dysplasia (RAEB-1) with monosomy 7 which rapidly transformed into AML in a patient with GIST during imatinib treatment.