Elena Cavalieri

Hodgkin’s Disease during Pregnancy: Diagnostic and Therapeutic Management

Objectives: To evaluate the possibility that women affected by Hodgkin’s disease (HD) during their second or third trimester of pregnancy can safely carry their pregnancy to term. Methods: From 1986 to 1997, 6 women came to our Center during the second trimester of pregnancy and were diagnosed as having HD. Three of these 6 patients were treated with chemotherapy before delivery and 3 of them were kept under observation and started treatment after delivery. Results: All 6 women gave birth to a healthy female. Conclusions: The pregnancy does not worsen the course of the illness and does not compromise long-term clinical remission and recovery.

A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by 90Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma

BACKGROUND A prospective, single-arm, open-label, multicenter, nonrandomised phase II trial to evaluate efficacy and safety of short fludarabine, mitoxantrone, and rituximab (FMR) induction followed by radioimmunotherapy, in untreated, intermediate/high-risk follicular non-Hodgkins lymphoma (NHL) patients. PATIENTS AND METHODS Fifty-five patients were treated using a sequential treatment schedule of four induction cycles of FMR chemoimmunotherapy, and a subsequent consolidating single administration of (90)Y-ibritumomab tiuxetan ((90)Y-IT), 8-14 weeks later. Patients were eligible for radioimmunotherapy if at least in partial response (PR) after induction, with normal platelet and granulocyte counts and a bone marrow infiltration ≤ 25%. Primary study end points were response rate and hematologic toxic effects; secondary end points were overall survival (OS) and progression-free survival (PFS). RESULTS All the 55 patients received four induction cycles with an overall response rate of 96% (38 complete responses [CR] and 15 PR). Fifty-one patients (38 in CR and 13 in PR) received (90)Y-IT. By the end of the treatment, 49/55 patients achieved a CR. With a median follow-up of 21 months, the estimated 3-year PFS was 81% and the 3-year OS 100%. CONCLUSIONS This study has established feasibility, tolerability, and efficacy of a regimen composed by short FMR induction with (90)Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.

Conventional salvage chemotherapy vs. high-dose therapy with autografting for recurrent or refractory Hodgkin's disease patients

Abstract Despite progress that has been made in curing Hodgkins disease (HD), patients whose first remission is brief and those resistant to first-line chemotherapy still have a poor outcome. We retrospectively reviewed data from 29 patients with HD in first relapse or refractory to first-line chemotherapy. Following failure, all patients received three cycles of ifosfomide, epirubicin, and etoposide (IEV); moreover, 11 patients received a conditioning regimen followed by autografting. Of the 18 patients treated with IEV, eight (44%) are alive; nine died of disease progression, and one died of hematologic toxicity. The 24-month overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) are 18%, 44%, and 22%, respectively. Of the 11 patients treated with IEV and autografting, ten are alive (90%) and one patient died of progressive disease. The 29-month OS, RFS, and EFS are 91%, 71%, and 56%, respectively. Our results confirm data showing that patients with relapsed or resistant HD achieve a significantly better OS and EFS if treated with high-dose therapy and autografting.

Use of interim [18F]fluorodeoxyglucose-positron emission tomography is not justified in diffuse large B-cell lymphoma during first-line immunochemotherapy

Abstract In diffuse large B-cell lymphoma (DLBCL), the response to first-line immunochemotherapy remains somewhat unpredictable. Interim [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) (PET-int) analysis could be an important tool in the prompt shift to intensified regimens. We prospectively evaluated the effectiveness of PET-int carried out at mid-treatment with standard immunochemotherapy in predicting relapse in a series of 85 consecutive patients with DLBCL. PET-int results were dichotomized as positive or negative using the recently validated five-point scale scoring system. This examination was also compared with interim computed tomography (CT-int) and final PET (PET-fin). End-points were: complete remission (CR), positive predictive value (PPV) of refractoriness and relapse, negative predictive value (NPV), overall survival (OS) and progression-free survival (PFS). Observation time was fixed to 24 months unless preceded by a DLBCL-related event. The PPV of PET-int was 58% and the NPV was 77%. CR was correlated with both PET-int and CT-int (p < 0.0001), but in multivariate analysis only CT-int was correlated with CR (p = 0.002). CT-int and PET-fin were predictive of both OS and PFS, whereas PET-int was predictive only of OS (p = 0.013). In Cox regression only PET-fin was predictive for both OS (p = 0.004) and PFS (p = 0.005). PET-int was unable to discriminate those chemosensitive patients who would later relapse. We therefore believe that the use of this expensive radioactive tool is not justified as an interim analysis.

Stage I/II follicular lymphoma: spread of bcl‐2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy

Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl‐2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66·6%). After treatment, in 9/15 Bcl‐2/IgH positive evaluable patients, a disappearance of Bcl‐2/IgH+ cells was observed, which persisted after a median follow‐up of 43·5 months (range 11–70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl‐2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl‐2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl‐2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR.

Efficacy of the BEACOPP regimen in refractory and relapsed Hodgkin lymphoma.

The BEACOPP regimen is a consolidated first-line treatment regimen for advanced stage Hodgkin lymphoma (HL), while few data are available on the efficacy of this regimen in advanced disease. About 50% of patients with HL relapsed after or refractory to first-line therapy achieve a durable response after peripheral blood stem cell transplantation (PBSCT). Patients relapsing after a PBSCT (performed as second line therapy) have a very poor prognosis. We evaluated the efficacy of BEACOPP in two settings: patients refractory or in relapse after first-line therapy (Group A) and patients relapsing after a PBSCT (Group B). Twenty-three patients with HL, admitted between February 2003 and April 2007, were retrospectively studied: 10 patients in Group A and 13 in Group B. Group A: Nine complete remissions (CR) and one partial remission (PR) were achieved following BEACOPP treatment. After a median follow-up of 32 months, one patient has died due to secondary leukemia, while the other eight are alive, five (50%) in second CR, three in third CR after PBSCT and one with disease. Group B: Eight of the 13 patients (62%) obtained a CR, one patient a PR, two were refractory and two have died of toxicity. To date, eight patients (62%) are alive, four (31%) still in CR. All patients experienced hematologic toxicity (WHO 3–4) with two deaths due to septic shock. These results show that BEACOPP is an effective regimen for both refractory/relapsed patients with HL after first-line treatment (Group A) and for patients relapsing after a PBSCT (Group B) with a 3-year probability of overall survival, progression-free survival, and cumulative incidence of relapse of 90, 50, and 33.3% in Group A, and 61, 31, and 37.5% in Group B, respectively.

Continuous Low Dose of Melphalan and Prednisone in Patients with Multiple Myeloma of Very Old Age or Severe Associated Disease

Introduction and ObjectiveThe management of elderly patients with multiple myeloma is a relevant problem because it concerns a great number of patients. Patients with multiple myeloma who are very old or who have severe associated diseases have a dismal outcome. For these patients we retrospectively evaluated the effect of a mild approach with continuous low-dose melphalan and prednisone (cMP).Design and Methods109 patients with multiple myeloma, observed between 1985 and 2000, were treated with cMP; 67 were treated at time of diagnosis (group A; median age 78 years) and 42 as a second or subsequent line of therapy (group B; median age 72 years). The toxicity of the treatment was compared with a control group of 29 patients aged over 70 years, treated in the same institution with the conventional cyclical melphalan/prednisone regimen.ResultsMajor or minor responses were obtained in 32% of patients in group A and 13% of patients in group B. Disease was stabilised in 45% of group A and 47% of group B and progressed in 5 and 18%, respectively. Median survival was, respectively, 19 and 24 months in group A and B.Among the 42 patients who received cMP as a second-line therapy (group B), 36 (86%) had previously been treated according to the standard cyclical melphalan/prednisone schedule; of these 12 (33%) obtained a better M protein reduction after cMP compared with the previous response to first-line cyclical melphalan/prednisone.The cMP schedule was generally well tolerated, and the rate of haematological toxicity was lower than for a historical control group receiving cyclical melphalan/prednisone.ConclusionThe cMP treatment schedule is well tolerated and results in a high proportion of patients with stable disease, with acceptable survival even in patients with advanced disease.

Nodular Lymphocyte-Predominant Hodgkin Lymphoma in a Warthin Tumor of the Parotid Gland: A Case Report and Literature Review.

Hodgkin lymphoma (HL) associated with Warthin tumor (WT) is extremely rare, accounting for only 3 cases of classical HLs. Here, we report for the first time the occurrence of a nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) involving the lymphoid stroma of a WT of the parotid gland. Pathogenesis of WT is controversial, with both a nodal and a parenchymal possible origin. On the other hand, extranodal involvement by HLs is uncommon. In our case, the coexistence of a WT and of a NLPHL within its stroma and in cervical lymph node emphasizes the importance of a careful evaluation of the lymphoid tissue in WT in order to exclude the possibility of an associated lymphoid malignancy.

Use of PCR for BCL2/IgH + cells in stage I/II follicular lymphoma to identify positive cells in bone marrow and peripheral blood that can be cleared by lymph-node irradiation

8571 Background: Stage I/IIA follicular lymphoma (FL) is considered a localized disease that can be adequately treated with radiotherapy alone. Minimal NHL contamination in peripheral blood (PB) or bone marrow (BM) can be detected by qualitative and quantitative PCR. Aim of this study was to evaluate the role of PCR, the impact of radiotherapy and prognosis in localized FL. Methods: BM and PB involvement in FL was investigated by PCR in a series of 25 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy alone. Results: Despite a negative BM biopsy, Bcl-2/IgH+ cells were found at diagnosis in the PB and/or BM of 17 patients (68%). After lymph-node involved field radiotherapy, in 10/16 Bcl-2/IgH positive, valuable patients, a disappearance of Bcl-2/IgH+ cells was observed, which persisted after a median follow-up of 42 months (range 5–79) in all but 2 patients.. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irr...