Beatrice Casadei

The addition of plerixafor is safe and allows adequate PBSC collection in multiple myeloma and lymphoma patients poor mobilizers after chemotherapy and G-CSF

We report 13 multiple myeloma (MM) or lymphoma patients who were failing PBSC mobilization after disease-specific chemotherapy and granulocyte-CSF (G-CSF), and received plerixafor to successfully collect PBSCs. Patients were considered poor mobilizers when the concentration of PB CD34+ cells was always lower than 10 cells/μL, during the recovery phase after chemotherapy and/or were predicted to have inadequate PBSC collection to proceed to autologous transplantation. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to three consecutive days, while continuing G-CSF, 10–11 h before the planned leukapheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a 4.7 median fold-increase in the number of circulating CD34+ cells after plerixafor as compared with baseline CD34+ cell concentration (from a median of 6.2 (range 1–12) to 21.5 (range 9–88) cells/μL). All patients collected >2 × 106 CD34+ cells/kg in 1–3 leukaphereses. In all, 5/13 patients have already undergone autograft with plerixafor-mobilized PBSCs, showing a rapid and durable hematological recovery. Our results suggest that the pre-emptive addition of plerixafor to G-CSF after chemotherapy is safe and may allow the rescue of lymphoma and MM patients, who need autologous transplantation but are failing PBSC mobilization.

Bortezomib as salvage treatment for heavily pretreated relapsed lymphoma patients: a multicenter retrospective study

Current treatments for non‐Hodgkin lymphomas are not optimally effective. Among new agents, bortezomib seems to play a pivotal role in the regulation of several cell pathways involved in the development of lymphomas. After results were obtained with clinical trials, we aimed to observe treatment with bortezomib in everyday clinical practice. We performed a multicenter retrospective analysis to assess the efficacy of bortezomib in heavily pretreated (median number of previous therapies 4, range 2–6) lymphoma patients in an off‐label setting. Bortezomib therapy was scheduled for 4–6 cycles (1.3 mg/m2 biweekly). Data from 50 patients were collected: 22% had a complete remission, 26% obtained a partial response and the remaining 52% was non‐responder. According to histotype, we observed an overall response rate (ORR) of 51.6% in mantle cell lymphomas, an ORR of 60% among follicular lymphoma patients, and an ORR of 50% in the indolent nonfollicular lymphomas. None of diffuse large B‐cell lymphoma patients obtained a response. Extra‐hematological toxicity was really mild, and peripheral neuropathy occurred in only 5 patients; hematological toxicity was grades 3–4 thrombocytopenia in nine patients and grades 3–4 neutropenia in only three patients. In conclusion, treatment with bortezomib as single agent resulted safe and effective in a subset of heavily pretreated lymphoma patients with usually poor outcome. New future hypotheses of investigation are indicated. Copyright

Prognostic Value of Interim Positron Emission Tomography in Patients With Peripheral T-Cell Lymphoma

The definition of the role of positron emission tomography (PET) in peripheral T-cell lymphomas (PTCLs) is still under investigation. The purpose of the present observational retrospective study was to assess the early prognostic value of PET after the first three cycles of therapy (PET+3), evaluating visual data in de novo PTCL patients treated in first line with standard chemotherapy and followed by both PET and computed tomography scan. Of 27 PET+3-negative patients, 19 also had a negative PET at the end of treatment (PET+6), whereas 8 of 27 had a positive final one; 6 of 7 PET+3-positive patients had a positive PET+6, whereas only 1 patient had a negative PET+6. Estimated overall survival plotted according to PET+3 results showed 78.6% for negative patients and 21.4% for positive patients at 88.7 months with a significant difference. Patients with negative PET+3 had superior progression-free survival of 72.6% compared with 16.7% of PET+3-positive patients. At the time of this analysis, 17 of 19 (89.5%) patients with negative PET+3 are in continuous complete response (CCR) and only 1 of 7 (14.2%) patients with positive PET+3 is still in CCR. In conclusion, our results indicate that positive PET+3 is predictive of a worse outcome in PTCL, and this significant statistical difference between the two curves could be clinically informative. Larger and prospective studies and harmonization of PET reading criteria are needed.

Complete Response of Relapsed Systemic and Cutaneous Anaplastic Large Cell Lymphoma Using Brentuximab Vedotin: 2 Case Reports

Clinical Practice Points Relapsed and refractory T-cell lymphomas represent a great challenge for clinicians because of their scarce tendency to show a response to further conventional treatments: in particular, for systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) treatment outcomes remain unknown and their potential benefits are still difficult assess. The conventional therapy in relapsed/refractory ALCL is poorly defined and no standard of care exists in this setting. It is difficult to obtain complete remissions using single-agent therapy. The wide expression of the CD30 antigen in ALCL cells makes this molecule a suitable target for monoclonal antibodies. In a phase II trial, the anti-CD30 monoclonal immunoconjugated brentuximab vedotin has shown an impressive effect in patients with relapsed ALKnegative ALCL, with high overall and complete response rates. Brentuximab vedotin is now approved by the Food and Drug Administration for the treatment of patients with relapsed ALCL, and now represents a valid treatment strategy for heavily pretreated patients.

The role of rituximab and positron emission tomography in the treatment of primary mediastinal large B-cell lymphoma: experience on 74 patients

Regarding primary mediastinal large B‐cell lymphoma (PMLBCL), there are several controversial topics that warrant further investigation: the superiority of third‐generation regimens, the impact of rituximab, the use of involved field radiotherapy (RT) and the assessment of clinical response by positron emission tomography (PET). We report our experience on 74 PMLBCL patients treated with a combination of a third‐generation chemotherapy regimen (MACOP‐B) and rituximab: an observational retrospective single‐centre study was conducted on patients diagnosed and treated between February 2002 and July 2011. All patients were evaluated by computed tomography scan and PET scan; after the final PET evaluation, PET‐negative patients were observed, whereas PET‐positive patients underwent mediastinal RT. Sixty‐one (82.4%) patients achieved a complete response after the MACOP‐B plus rituximab regimen; 68.9% presented a positive final PET and were treated with local RT, whereas 31.1% had a negative PET. Five patients relapsed within 12 months. At 10 years, overall survival was 82%, progression‐free survival was 87.6% and disease‐free survival (DFS) was 90.5% (median follow‐up 4 years). No statistically significant differences were observed in DFS between the patients treated also with RT (PET positive) and patients only observed (PET negative): 90.7% vs 90% (p = 0.85), respectively. In our experience, adding rituximab does not change the final results in terms of complete response and DFS utilizing third‐generation regimen. Furthermore, the introduction of the PET‐guided RT approach leads to a patient‐tailored treatment, which preserves the outcome and, at the same time, allows reducing the use of RT. Copyright

Non-Hodgkin Lymphomas Presenting as Soft Tissue Masses: A Single Center Experience and Meta-Analysis of the Published Series

BACKGROUND Lymphomas with involvement of soft tissues as a primary event are very rare. The published studies have a small sample size, most of them being reported as case reports. PATIENTS AND METHODS In this article we describe our experience with soft tissue non-Hodgkin lymphomas (NHL) diagnosed and treated in our institution over a 15-year period. Moreover, we systematically review the available data from the literature in the past 2 decades, considering all the published series and case reports available from 1990 to 2011 using a PubMed access. RESULTS In the monocentric analysis, 16 consecutive patients treated at our Institution from 1996 to 2011 were considered. In the literature search, we selected 16 case reports (18 patients) and 5 case series (49 patients), including a total of 67 patients. Eighty-three patients were finally considered in the combined analysis. The most common histologic subtype was diffuse large B cell lymphoma (DLBCL) (>50% of cases in both groups). In both analyses we observed an inferior outcome for DLBCL compared with indolent B-cell NHL (5-year progression free survival: 34% vs. 64%, respectively, in the combined analysis; P = .01). Furthermore, the prognosis in the DLBCL group appears to be worse compared with the historical data of DLBCL patients treated with chemoimmunotherapy. CONCLUSIONS Though indolent soft tissue B-cell NHLs appear to have a good outcome, soft tissue DLBCLs represent an anatomic-clinical entity with aggressive features, and dismal prognosis. Strategies of first-line therapy intensification could be considered. Studies aiming to a better biologic characterization of this peculiar entity are warranted.

Collection of Hematopoietic Stem Cells after Previous Radioimmunotherapy is Feasible and Does Not Impair Engraftment after Autologous Stem Cell Transplantation in Follicular Lymphoma

Major concerns about radioimmunotherapy (RIT) administration early in the course of follicular lymphoma (FL) are long-term toxicity and the theoretical impairment of hematopoietic stem cell (HSC) harvest, but few data are available about mobilization rates after RIT. This study evaluates the impact of prior therapy with RIT (yttrium-90 ibritumomab tiuxetan) and different chemotherapy regimens in all FL patients (N = 103) attempting HSC mobilization at our institution over the last 7 years. Sixty-nine patients received R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone) or CHOP-like regimens, 21 patients received R-FM (rituximab-fludarabine-mitoxantrone), and 13 patients received RIT before HSC mobilization. Median CD34+ cell yield at first mobilization was 7.2 × 10(6)/kg in the R-CHOP group versus 4.3 in the R-FM group versus 1.7 in the RIT group (P = .02 R-CHOP versus R-FM; P < .0001 R-CHOP versus RIT; P < .02 R-FM versus RIT). Although 8 of 13 patients initially failed to collect enough HSC after RIT, a second and/or salvage harvest was successfully performed in 7 patients, with 10 of 13 patients (77%) finally undergoing autologous stem cell transplantation (ASCT). No differences in engraftment kinetics were observed between the three groups (R-CHOP versus R-FM versus RIT). Although mobilization was significantly impaired in patients previously treated with RIT, a salvage HSC harvest and ASCT after RIT were safe and feasible in most patients.

Long-term efficacy and toxicity results of the FLUMIZ trial (fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in untreated follicular lymphoma)

The radiosensitivity of lymphomas as well as the local targeted delivery of high doses of radiation make radioimmunotherapy (RIT) an attractive therapeutic option. RIT is indeed an underestimated tool. In follicular lymphoma (FL), RIT represents one of the most effective single agents. The two most commonly used radioimmunoconjugates are Y-ibritumomab tiuxetan (Zevalin ) and I-tositumomab, both based on murine anti-Cd20 antibodies. Annals of Oncology letters to the editor

Fludarabine-mitoxantrone-rituximab regimen in untreated intermediate/high-risk follicular non-Hodgkin's lymphoma: experience on 142 patients.

There is no international consensus on front‐line optimal chemotherapy regimen for advanced stage follicular lymphoma (FL) patients, or a clear definition of cure for this disease. Aim of this study was to test the degree of effectiveness and the safety of the regimen containing fludarabine, mitoxantrone, and rituximab in a subset of poor prognosis FL patients with particular focus on the long‐term disease‐free survival. A retrospective study was conducted on 142 intermediate/high‐risk FL patients treated in first‐line with fludarabine, mitoxantrone, and rituximab regimen. Responses, safety, and survival were evaluated. The prognostic value of positron emission tomography (PET) was also investigated in a 56‐patients subset. Overall response rate was 95.5% including 88% of complete responses. With a median follow‐up of 48 months, 18% of patients had disease relapse, yielding an estimated 12‐year disease‐free survival (DFS) of 72%. All cases showed the lymphoma recurrence within 40 months: after this timing the DFS curve presented a plateau. Overall survival was 73% at 12 years. Post‐treatment PET positivity remains a highly significant predictor of disease progression. The observed high rate of complete responses following the use of fludarabine, mitoxantrone‐based regimen in combination with rituximab seems to be the first step to improve DFS. Our study could be the starting point to consider DFS as a potential alternative endpoint of future clinical trials on FL patients. Am. J. Heamtol. 88:E273–E276, 2013.

Hairy Cell Leukemia: Allogeneic Transplantation Could be an Optimal Option in Selected Patients

Introduction Over the past 30 years, we have obtained remarkable progress in the treatment of patients with hairy cell leukemia (HCL). Despite his, the disease-free survival after effective therapy (purine nucleoide analogues) has not reached a plateau, suggesting control rather han cure of the disease. Combined chemoimmunotherapy may be onsidered the most promising treatment for disease eradication, but he optimal strategy for using this approach is still under active nvestigation. We report the case of a patient with HCL who was treated with everal therapeutic approaches including pentostatin, cladribine, inerferon-alpha (IFN), and rituximab during the 11 years of his isease history. After disease progression, the patient was successfully reated with allogeneic stem cell transplantation (allo-SCT), achievng a clinical remission.