Rita Mazza

Predictive value of early 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high‐dose chemotherapy

This retrospective study evaluated whether early 2‐[fluorine‐18]fluoro‐2‐deoxy‐D‐glucose positron emission tomography (FDG‐PET) after two cycles of salvage chemotherapy (PET2) could predict survival after high‐dose chemotherapy (HDC). Twenty‐four Hodgkin lymphoma (HL) patients were included. PET2 was negative in 58% and positive in 42% of patients. Ninety per cent of patients (9/10) with positive PET2 relapsed after HDC while all but one patient with negative PET2 maintained a complete remission. The 2‐year progression‐free survival was 93% vs. 10% for patients with negative and positive PET2, respectively (P < 0.001). This study shows that interim PET can predict the outcome after high‐dose chemotherapy in HL patients.

Acute megakaryocytic leukemia in essential thrombocythemia: an unusual evolution?

Abstract: Essential thrombocythemia (ET) is a chronic myeloproliferative disorder that can rarely undergo leukemic transformation either in treated (3–7%) or untreated patients (1%). Evolution to myeloblastic or myelomonoblastic acute leukemia is commonly described in the literature, whereas lymphatic and megakaryocytic forms are considered unusual. Here, we report three cases of acute megakaryocytic leukemia (LMA‐M7) among 11 acute leukemic transformations observed in our series of 321 ET patients. LMA‐M7 was diagnosed employing immunophenotyping according to FAB criteria. These recurrences of LMA M7 suggest that this kind of evolution cannot be considered rare or casual in ET.

Reduced-intensity allogeneic transplantation in patients with refractory or progressive Hodgkin's disease after high-dose chemotherapy and autologous stem cell infusion

Background: We analysed the feasibility and efficacy of allogeneic stem cell transplantation (allo‐SCT) with reduced‐intensity conditioning (RIC) in patients with refractory or progressive Hodgkins disease (HD) after high‐dose chemotherapy (HDCT). Patients and methods: Fourteen patients with HD received allo‐SCT with RIC: eleven patients had a human leucocytes antigen‐identical related donor and three a matched unrelated donor. Six had chemoresistant disease and eight had chemosensitive one at the time of transplantation. All patients received a fludarabine‐based RIC. Results: All patients engrafted and full donor chimerism was achieved in all patients. Grade II acute graft‐vs.‐host disease (GvHD) developed in six of the 14 patients (43%). Chronic GvHD developed in eight of the 13 patients (61%). There was neither early nor late treatment‐related mortality (TRM). With a median follow‐up of 21 months (range 3–74), 10 of the 14 patients were alive (71%). Estimated overall survival at 1 and 2 yr was 93% and 73%, respectively, for the whole population, 83% and 44% respectively for patients with chemoresistant disease and 100% for those with chemosensitive disease. Estimated progression‐free survival at 1 yr was 36%; 62.5% for chemosensitive patients and 0% for those with chemoresistant disease. Conclusions: In conclusion, allo‐SCT with fludarabine‐based RIC is a feasible procedure, without TRM in HD patients relapsed and refractory after HDCT. Even if several questions are still open, this approach should proposed for these poor prognosis patients.

Early discharge after high-dose melphalan and peripheral blood stem cell reinfusion in patients with hematological and non-hematological disease

The purpose of this study was to analyse our experience of early discharge 2 days after high-dose melphalan (HDM) (Day-1) followed by peripheral blood stem cell re-infusion (Day-0) and re-admission on Day +5 in patients with hematological diseases or solid tumors. From 2000 to November 2005, seven patients received tandem Melphalan 200 mg/m2 HDM with peripheral blood stem cells transplantation (PBSC-T), 130 a single HDM, for a total of 144 procedures. In 123 of them, patients were discharged on Day +1 for re-admission on Day +5 or earlier in the event of complications. Antibiotic prophylaxis was not used. Patients were hospitalised in positive-pressure reverse isolation room during the neutropenic period. Of the 123 procedures eligible for our mixed inpatient–outpatient management regimen, six (5%) required early re-admission for complications. Full engraftment was achieved in all cases. Median time to neutrophil count >0.5 × 109/µL and >1 × 109/µL were 12 and 14 days, respectively. Median time to platelet recovery (>20 × 109/µL) was 13 days. Severe extra-hematological toxicities occurred in 78 (63%) patients: all had oral mucositis and five had associated diarrhoea. During hospitalisation, 94/123 (76%) experienced febrile neutropenia, 20/94 (21%) had documented infection and 74/94 (79%) were considered fever of unknown origin. Median fever duration was 1 day (range 0–11). Median duration of antibiotic treatment was 6 days (range 3–26). Median time to discharge (from Day 0) was 16 days (range 11–57). There was no mortality by on Day +100. Our experience of early discharge after HDM and PBSC-T with re-admission on Day +5 is safe and feasible with acceptable frequency of hematological and extra-hematological toxicities. The regimen allows reduced hospital stay and hence cost savings.

Inhibition of chronic graft-vs-host disease with retention of anti-myeloma effects by the proteasome inhibitor bortezomib.

Graft-vs-host-disease (GVHD) is a major complication of allogeneic stem cell transplantation (ASCT) [1]. Bortezomib is a proteasome inhibitor that has recently been approved for myeloma treatment. It has been shown to have numerous biological effects, including inhibition of NF-kB activation [2]. NF-kB is a transcription factor that has been detected in most cell types and that controls the expression of a number of genes involved in mediating immune and inflammatory responses [3]. A recent study on murine acute graft-vs-host disease (aGVHD) models has shown that bortezomib induces a selective depletion of alloreactive T lymphocytes by decreasing the production of Th1 cytokines [4]; it inhibits aGVHD and preserves graft-versus-tumor (GVT) effects [5]; and also that NF-kB is the target of bortezomib activity for aGVHD prevention [6]. However, there are only sparse data available on the effect of bortezomib on human GVHD [7]. We report a case of extensive chronic GVHD (cGVHD) and post-ASCT extramedullary myeloma progression, which were both responsive to bortezomib. A 49-year-old Caucasian patient with IgGk Stage III A multiple myeloma (Durie and Salmon) upon diagnosis, in partial remission because of a persistent positive immunofixation [8] after conventional chemotherapy and high-dose melphalan, received lenograstim-stimulated CD34þ cells from an HLAidentical sibling (on Day 0) after reduced-intensity conditioning with fludarabine 30 mg/m/die 73, 72, 71 i.v. and cyclophosphamide 300 mg/m/die 73, 72, 71 i.v. GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. Neutropenia and thrombocytopenia were not observed. Disease evaluation after ASCT showed stable disease. Full donor chimerism (revealed by PCR analysis) on total marrow and peripheral cells was reached six months after transplant and coincided with cyclosporine withdrawal. Eight months after ASCT the patient developed extensive cGvHD with involvement of the liver, skin, and bilateral conjunctiva and mouth mucosa, which was treated with cyclosporine and steroids until complete remission was reached. Sixteen months after ASCT the patient experienced extramedullary disease progression as revealed by a huge mass (12.56 9 cm) extending to the upper left chest wall, reappearance of monoclonal immunoglobulin (M component) by electrophoresis, and absence of bone marrow infiltration by plasma cells. The chest mass biopsy confirmed the presence of myelomatous cells. Cyclosporine was tapered and stopped, and loco-regional radiotherapy (total 20 Gy) was administered without any disease response. Then the patient received three monthly escalating doses of donor lymphocytes (DLIs, 16 10 kg; 56 10 kg; 16 10 kg) from his HLA-identical donor without any perceivable reduction of the extramedullary mass. Therefore, in June 2005, a few days after the third DLI, he was started on standard-dose bortezomib (1.3 mg/m i.v. for four times on Days þ1, þ4, þ8, þ11) to be

CD34+ dose‐driven administration of granulocyte colony‐stimulating factor after high‐dose chemotherapy in lymphoma patients

Our goal was to optimize use of granulocyte colony‐stimulating factor (G‐CSF) after high‐dose chemotherapy and autologous peripheral blood stem‐cell transplantation in lymphoma patients, limiting G‐CSF administration to patients infusing a suboptimal CD34+ cell number. Of 124 consecutive patients with histologically proven Hodgkins and non‐Hodgkins lymphoma from January 2001 to June 2004, 60 patients (group 1) given ≥5 × 106/kg CD34+ cells received no G‐CSF; 64 patients (group 2) given ≤5 × 106/kg CD34+ cells received G‐CSF from day +5 after stem‐cell reinfusion. The median times to reach 0.5 × 109/L and 1.0 × 109/L neutrophils were, respectively, 3 and 4 d shorter in G‐CSF group and this difference was statistically significant (P = 0.0014; P = 0.0001). In terms of antibiotic and antimycotic requirements, gastrointestinal toxicity, days of hospitalization, and transfusion requirements, no differences were demonstrated between the two groups. No statistically significant difference was demonstrated for the total number of febrile episodes (52 for group 1; 53 for group 2; P = 0.623) and the median number of febrile days (2 d for both groups). Myeloid reconstitution values for both groups agree with published results for autotransplanted patients treated with G‐CSF from 7 to 14 d. Also, major clinical events, antibiotic, antimycotic, and transfusion requirements, and hospital stay were similar to published findings. Our data suggest that G‐CSF administration can be safely optimized, used only for patients infused with a suboptimal CD34+ cell dose.

B-IGEV (bortezomib plus IGEV) versus IGEV before high-dose chemotherapy followed by autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: a randomized, phase II trial of the Fondazione Italiana Linfomi (FIL).

Abstract This randomized, multicenter study evaluates the addition of bortezomib (13 mg/m2) to IGEV (B-IGEV) in patients with relapsed/refractory Hodgkin Lymphoma (HL). Patients received either four courses of IGEV alone (n = 40) or B-IGEV (n = 40). The primary endpoint was the complete response (CR) proportion, evaluated by FDG-PET, after induction chemotherapy. CR proportion was 39% with B-IGEV and 53% with IGEV. PFS and OS were similar between the two groups (two-year PFS: 58% vs 56%; two-year OS: 93% vs 81%). The PET-negative status after treatment was the only variable favorably influencing both PFS (two-year PFS: 77% vs 40%; p = 0.002) and OS (two-year OS: 100% vs 76%; p < 0.001). Toxicity was overall similar with the two regimens. The addition of bortezomib to IGEV does not improve response in relapsed/refractory HL patients. However, its favorable therapeutic and safety profile, and the prognostic role of pre-transplant PET negativity in patients receiving IGEV-based regimens are confirmed.

Bendamustine in Combination with Gemcitabine and Vinorelbine (BEGEV) is an Effective Regimen for Heavily Pretreated, Relapsed or Refractory Hodgkin Lymphoma Patients: A Retrospective Study

S234 HL-238 Bendamustine in Combination with Gemcitabine and Vinorelbine (BEGEV) is an Effective Regimen for Heavily Pretreated, Relapsed or Refractory Hodgkin Lymphoma Patients: A Retrospective Study Antonio Russo , Francesca Ricci, Massimo Magagnoli, Marcello Rodari, Lucia Morello, Rita Mazza, Arturo Chiti, Luca Castagna, Armando Santoro, Carmelo Carlo-Stella Oncology and Hematology, Humanitas Cancer Center, Humanitas Research Hospital, Milan, Italy; Nuclear Medicine, Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy