Fiammetta Natalino

MACOP-B and Involved-Field Radiotherapy Is an Effective and Safe Therapy for Primary Mediastinal Large B Cell Lymphoma

PURPOSE To report the clinical findings and long-term results of front-line, third-generation MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin) chemotherapy and mediastinal involved-field radiotherapy (IFRT) in 85 consecutive, previously untreated patients with primary mediastinal large B cell lymphoma (PMLBCL) diagnosed and managed at a single institution. METHODS AND MATERIALS Between 1991 and April 2004, 92 consecutive, untreated patients with PMLBCL were treated at our institution. The median age was 33 years (range, 15-61 years), 46 patients (50%) showed a mediastinal syndrome at onset; 52 patients (57%) showed a low/low-intermediate (0 to 1) and 40 patients (43%) an intermediate-high/high (2 to 3) International Prognostic Index (IPI) score. Eighty-five patients were treated with standard chemotherapy (MACOP-B), and 80 underwent mediastinal IFRT at a dose of 30-36 Gy. RESULTS After a MACOP-B regimen, the overall response rate was 87% and the partial response rate 9%. After chemotherapy, (67)Ga scintigraphy/positron emission tomography results were positive in 43 of 52 patients (83%), whereas after IFRT 11 of 52 patients (21%) remained positive (p < 0.0001). After a median follow-up of 81 months (range, 2-196 months), progression or relapse was observed in 15 of 84 patients (18%). The projected 5-year overall survival and progression-free survival rates were 87% and 81%, respectively. The 5-year overall survival and progression-free survival rates were better for patients with an IPI of 0 to 1 than for those with an IPI of 2 to 3 (96% vs. 73% [p = 0.002] and 90% vs. 67% [p = 0.007], respectively). CONCLUSIONS Combined-modality treatment with intensive chemotherapy plus mediastinal IFRT induces high response and lymphoma-free survival rates. Involved-field RT plays an important role in inducing negative results on (67)Ga scintigraphy/positron emission tomography in patients responsive to chemotherapy.

Selective splenic artery embolization for the treatment of thrombocytopenia and hypersplenism in paroxysmal nocturnal hemoglobinuria.

BackgroundPNH is associated with abdominal vein thrombosis, which can cause splenomegaly and hypersplenism. The combination of thrombosis, splenomegaly, and thrombocytopenia (TST) is challenging because anticoagulants are indicated but thrombocytopenia may increase the bleeding risk. Splenectomy could alleviate thrombocytopenia and reduce portal pressure, but it can cause post-operative thromboses and opportunistic infections. We therefore sought to determine whether selective splenic artery embolization (SSAE) is a safe and effective alternative to splenectomy for TST in patients with PNH.MethodsFour patients with PNH and TST received successive rounds of SSAE. By targeting distal vessels for occlusion, we aimed to infarct approximately 1/3 of the spleen with each procedure.ResultsThree of 4 patients had an improvement in their platelet count, and 3 of 3 had major improvement in abdominal pain/discomfort. The one patient whose platelet count did not respond had developed marrow failure, and she did well with an allo-SCT. Post-procedure pain and fever were common and manageable; only one patient developed a loculated pleural effusion requiring drainage. One patient, who had had only a partial response to eculizumab, responded to SSAE not only with an improved platelet count, but also with an increase in hemoglobin level and decreased transfusion requirement.ConclusionsThese data indicate that SSAE can decrease spleen size and reverse hypersplenism, without exposing the patient to the complications of splenectomy. In addition, SSAE probably reduces the uptake of opsonised red cells in patients who have had a limited response to eculizumab, resulting in an improved quality of life for selected patients.

The immune reconstitution after an allogeneic stem cell transplant correlates with the risk of graft-versus-host disease and cytomegalovirus infection

Aim of the study was to correlate the clinical outcome of eighteen patients who have undergone an allogeneic stem cell transplant (SCT) with the concentration in the peripheral blood (PB) of lymphocyte subpopulations evaluated at 1 year from transplant. The occurrence of acute GVHD and CMV infection correlated with the concentration of Tregs in the PB; CMV infection also correlated with the content of NK cells. The obtained results document that the concentration of Tregs in the PB after an allogeneic SCT may protect from GVHD and from CMV infection; the potential anti-viral role of NK cells is confirmed.

Early onset of posterior reversible encephalopathy syndrome (PRES) during Cyclosporine-A infusion.

Posterior reversible encephalopathy syndrome (PRES) is an ncommon but distinctive clinico-radiologic entity characterized y headache, seizures, visual disturbance and altered mental funcion associated with reversible white matter edema affecting the osterior parietal and occipital lobes of the brain [1,2]. Etioloies of PRES include hypertension, cytotoxic medications, sepsis, reeclampsia or eclampsia and multiple organ dysfunction [3]. In he context of allogeneic stem cell transplantation (HSCT), severe eurotoxicity is reported in a substantial number of patients, being yclosporine-A (CSA) most frequently indicated as the medication esponsible for the neurological alterations [4–6].

Refractory Anaemia with Excess of Blasts in Transformation Re-Evaluated with the WHO Criteria: Identification of Subgroups with Different Survival

One of the major changes suggested by the World Health Organization (WHO) classification with respect to the French-American-British (FAB) proposal for myelodysplastic syndromes (MDS) was to lower the bone marrow (BM) blast count from 30 to 20%, thus eliminating the refractory anaemia with excess of blasts in transformation (RAEB-t) category. However, a general consensus has not been reached, and several authors still retain RAEB-t as an MDS sub-entity. We re-evaluated our series of 74 patients classified as RAEB-t according to the FAB criteria by stratifying them into two subsets: patients with at least 5% peripheral blast (PB) cells but with BM blasts <20% (group I) and patients with BM blastosis between 20 and 30% and PBs <5% (group II). We found differences among the two groups regarding sex, haematological parameters at presentation (white blood cell and neutrophil counts, haemoglobin level) and frequency of infectious episodes during the course of disease. We did not find differences as to the frequency of acute myeloid leukaemia transformation, but a significant difference was evidenced as to survival (9.3 vs. 16 months in group I vs. group II, respectively; p = 0.02). Furthermore, at our institution, we compared the RAEB-t group I patients who, based on >5% PBs, should be included in the RAEB-II category according to the WHO criteria, with a group of 98 patients who were diagnosed as RAEB-II according to the WHO criteria. The findings showed that the aggregation of these two subsets appeared inappropriate, because patients of the two groups showed different clinical features and rates of acute transformation. In conclusion, the RAEB-t entity according to the FAB criteria, although including heterogeneous clinical patient subsets, should more likely be considered as an advanced stage of MDS, rather than a true acute myeloid leukaemia.

Pregnancy in patients with myelodysplastic syndromes (MDS)

We report 6 pregnancies in 5 females with low-risk myelodysplastic syndromes (MDS) (median age at diagnosis 28 years, range 26-29) observed in the last 15 years. In 2 cases pregnancy was concomitant to the diagnosis of MDS, in the remaining 4 cases the intervals from diagnosis were 2, 3, 4 and 9 years, respectively. One patient had a foetal growth retardation corrected with steroid treatment while the remaining 5 pregnancies were uneventful. After a median time from delivery of 104 months (range 18-187) none of the patients developed acute myeloid leukemia (AML) and all are alive in stable disease. In conclusion, selected females with low-risk MDS could not be discouraged to have full term pregnancies.

Clinical responses in allografted acute leukaemia patients with resistant disease using a combined chemo‐immunotherapeutic treatment strategy

Induction of a graft-versus-leukaemia (GVL) immunological response is the key element for the success of the allogeneic haematopoietic stem cell transplant (SCT) procedure. This was first shown by the durable remissions induced by donor lymphocyte infusion (DLI) in relapsed chronic myeloid leukaemia (CML) patients (Kolb et al, 1995). For patients affected by non-CML haematological malignancies, however, this immunological approach is not always successful (Collins et al, 1997; Dermime et al, 1997). Different strategies have been conceived to overcome tumour resistance to donor lymphocytes. Chemotherapy is particularly attractive for both its cytoreductive and immune-potentiating activities (Emens et al, 2001), including provision of lymphoid space, elimination of host anti-donor immune reactivity, suppression of regulatory T cells and induction of activating cytokines (Klebanoff et al, 2005; Rapoport et al, 2005). Animal models of tumour-bearing mice demonstrated that the serum peak concentrations of activating cytokines and growth factors was reached 48 h after a cyclophosphamide-based treatment (Proietti et al, 1998; Bracci et al, 2007). In humans, it has been reported that a fully lymphodepleting chemotherapeutic treatment prior to DLI induces a significant increment of high grade acute graft-versushost disease (GVHD) (Miller et al, 2007), suggesting the possibility of enhancing the anti-tumour efficacy of donor lymphocytes. The present study aimed to analyse the immunological and clinical effects of a chemo-immunotherapeutic treatment strategy consisting of chemotherapy followed 48 h later by DLI in allografted acute leukaemia patients. Four patients with acute myeloid leukaemia (AML) that evolved from a myelodysplastic syndrome (MDS) and two