Savina Maria Luciana Aversa

Regression of AIDS-related Kaposi's sarcoma following antiretroviral therapy with protease inhibitors: biological correlates of clinical outcome

The clinical response of AIDS-related Kaposis sarcoma (KS) to highly active antiretroviral therapy (HAART), a combination of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase inhibitors, was studied in 11 patients, all but one with progressive KS. CD4+ cell counts, plasma HIV-1 RNA levels, and antibody titres to lytic ORF65 and latency-associated human herpes virus type 8 (HHV-8) proteins were determined in sequential samples. Six complete and three partial clinical responses were achieved in a median time of 6 and 3 months, respectively, and confirmed after a median time of 16 months on HAART. 2 patients showed disease progression. A consistent decrease in HIV-1 RNA levels, paralleled by an increase in CD4+ cell counts, was observed in all patients who showed complete or partial clinical response; HIV-1 RNA levels remained persistently high in the two patients who progressed, despite a change in HAART. HHV-8 antibody titres were generally higher in patients with mucosal/visceral involvement compared with patients with limited disease; a decrease in ORF65 antibody titre was significantly associated with a clinical response. These results indicate that HAART is effective for AIDS-related KS; the clinical response correlates with a decrease in plasma HIV-1 RNA levels, an increase in CD4+ lymphocytes, and a decrease in antibodies to ORF65 HHV-8 protein.

Stanford V Regimen plus Consolidative Radiotherapy Is an Effective Therapeutic Program for Bulky or Advanced-Stage Hodgkin’s Disease

Since September 1996, 48 untreated patients with bulky or advanced-stage Hodgkin’s disease received the 12-week Stanford V chemotherapy regimen followed by consolidation radiotherapy at a dose of 36 Gy to bulky mediastinal disease and 30.6 Gy to the initial sites of disease ≧3 cm in transverse diameter. After the combined therapy, 46 of 48 (96%) achieved complete remissions. With a median follow-up of 48 months, the 5-year overall survival was 95% and freedom from progression 86%.There were no treatment-related deaths. All but one premenopausal female patient (who received pelvic and inguinal irradiation) recovered normal menses. Until now no case of secondary leukemia or myelodysplasia was observed. Our results confirm that the Stanford V regimen with consolidation radiotherapy is safe and effective in patients with bulky or advanced-stage Hodgkin’s disease, achieving very high remission and overall 5-year survival rates. Longer follow-up is necessary to evaluate the extent of all complications.

Intrathecal chemotherapy in lymphomatous meningitis

Central Nervous System (CNS) involvement in lymphoma can occur whether at diagnosis or, more often, at the progression or recurrence of disease and the most frequent clinical manifestation is lymphomatous meningitis (LM). The first risk factor for LM development is the histotype, with the highest incidence for highly aggressive non-Hodgkins lymphomas (NHL) such as Burkitts lymphoma (BL) and lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and the lowest for indolent NHL. LM prophylaxis in aggressive NHL (other than BL and LBL/ALL) is a much debated question, because the identification of specific risk factors remains controversial. Moreover, there is not a consensus if the LM prophylaxis should consist of systemic chemotherapy (CT), intrathecal (i.t.) CT or both. In case of LM, the i.t. CT has a key role, but there is not a consensus on treatment schedule. Newer intensified regimens and rituximab lead to reconsider the whole approach to LM.

CHEMO-IMMUNOTHERAPY OF ADVANCED AIDS-RELATED KAPOSI'S SARCOMA

Aims and background Kaposis sarcoma (KS) is the most common neoplastic complication of HIV infection and AIDS. Multiple cytotoxic chemotherapy regimens have been used with various response rates. We have evaluated the efficacy and toxicity of low-dose chemotherapy in patients with poor-prognosis AIDS-related KS and the role of interferon alpha (IFN-α) in complete responders. Methods Twenty-five previously untreated patients with advanced KS received bleomycin (BL) 10 mg/m2 and vinblastine (VB) 6 mg/m2 on days 1 and 15 every two weeks. After six cycles, patients in complete remission received IFN-alpha (3 million U s.c. 3 times/week) combined with antiretroviral therapy. All patients were evaluated for toxicity using the World Health Organization (WHO) toxicity schedule. Both Eastern Cooperative Oncology Group (ECOG) and AIDS Clinical Trials Group (ACTG) response criteria were used to evaluate response and survival. Results The overall response rate was 84% (95% confidence interval, 51–117%) with six complete remissions (24%) and 15 partial remissions (60%) by ECOG criteria, and 92% (95% confidence interval: 58–128%) with 17 partial remissions (68%) by ACTG criteria. The median duration of response on IFN-alpha treatment was 4.5 months (range, 2–10). The overall median survival duration for all 25 patients was 9 months (range, 2–39). Grade 3–4 anemia was observed in five patients and grade 3–4 neutropenia in two patients. No other clinically significant (> grade 3) toxicities were observed. Conclusions Combination of BL and VB is effective and well tolerated, even if new therapeutic options are developing. This disease remains a challenging problem, so larger studies using the combination of chemotherapy and/or IFN-alpha with antiretroviral treatment are warranted.

Respiratory syncytial virus-related pneumonia after stem cell transplantation successfully treated with palivizumab and steroid therapy

A case is reported of a 56-y-old woman with a second relapse of Hodgkins disease who early developed after autologous stem cell transplantation (ASCT) a severe RSV-related interstitial pneumonia successfully treated with 1-d intravenous palivizumab 8 mg/kg plus low-dose systemic steroid therapy. B-cells suppression with CMV antigenaemia were then observed and required treatment with ganciclovir and liposomal amfotericine B.

Acute promyelocytic leukemia after Stanford V plus radiotherapy for advanced Hodgkin lymphoma

ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) is considered the standard treatment for advanced Hodgkin lymphoma. However, pulmonary and cardiac toxicity rates due to bleomycin and adriamycin, increased by mediastinal irradiation, and treatment failures (about 25%) prompted the development of new regimens, including BEACOPP [1] and Stanford V [2]. The Stanford V regimen, followed by consolidation involved-field (IF) radiotherapy (RT) was designed to maximise dose intensity reducing the total dose of adriamycin (to 150 mg/m), bleomycin (to 30 U/m), nitrogen mustard (to 18 mg/m), avoiding procarbazine. Preliminary reports showed that the Stanford V regimen with RT was well tolerated and effective for bulky, advanced-stage Hodgkin lymphoma [2]. These results were confirmed by several studies [3,4], the latest one performed by Nebraska Lymphoma Study Group [5]. The long-term survivors from Hodgkin lymphoma are at risk for second malignancies (solid tumors, leukemia and non-Hodgkin lymphoma) that account for the majority of late deaths [1]. When compared with the general population, the risk of myelodysplasia and secondary acute leukemia is increased 10to 80-fold and it appears to be related to the total dose of alkylating agents and DNA topoisomerase-II inhibitors. The cumulative risk of secondary leukemia varies from 6 to 9% after MOPP regimen; 2.5% after the escalated BEACOPP regimen and 0.5% after the standard ABVD. We report a case of acute leukemia in a 28-year-old woman who was treated for Hodgkin lymphoma with Stanford V regimen followed by radiotherapy. In September 1999, the patient was first diagnosed with a IIB, non bulky, subdiaphragmatic, mixed cellularity Hodgkin lymphoma. Bone marrow examination was normal. In October 1999, Stanford V chemotherapy was administered for 10 weeks instead of the planned 12 weeks followed by subdiaphragmatic involved-field radiotherapy; chemotherapy was stopped earlier because of grade 4 constipation. During the neutropenic phases, the patient received G-CSF. The whole treatment was completed in May 2000. The patient achieved a complete remission and enjoyed good health for 4 years. In September 2004, she was admitted to the Department of Hematology with a disseminated intravascular coagulation. Hemoglobin was 97 g/L, white blood cell count was 86.36 10/L, platelet count 116 10/L, LDH 698 U/L. The diagnosis of Acute Promyelocytic Leukemia (APL) was established upon examination of both peripheral blood and bone marrow smears. The blasts had the following

Treatment of non-Hodgkin's lymphoma in the elderly. The Italian studies.

Elderly patients constitute a significant proportion of patients with Non-Hodgkins Lymphoma (NHL). They generally have poorer prognosis than their younger counterparts. The International NHL prognostic factor project, although based on series of patients prevalently younger than 65 years, found that age is the most important prognostic factor. Inferior outcomes in elderly patients may result from the use of lower doses of chemotherapy and consequently poorer disease control, from increased susceptibility to the toxic effects of chemotherapy and more treatment related deaths, and from an increased prevalence of comorbidity with more deaths from causes unrelated to lymphoma. Apparently unrelated deaths can occur both on and off therapy. Two different therapeutic approaches have been adopted for elderly patients. The first one favors the use of standard treatments, unless severe comorbidity conditions are present. The second approach intends to utilize regimes specifically designed for elderly patients.

Radiotherapy alone in the treatment of clinical stage I-IIA, nonbulky, Hodgkin's disease: Single-institution experience on 73 patients staged with lymphangiography and laparoscopy

From 1985 to 1998, at the Regional Cancer Center of Padua, patients with Hodgkin’s disease (HD) routinely underwent a clinical staging procedure including lymphangiography and laparoscopy with multiple liver and spleen biopsies. Patients with IA and IIA nonbulky HD were treated with radiotherapy alone. The aim of this study is to analyze the efficacy of radiotherapy as radical treatment in this group of patients, and the role of lymphangiography and laparoscopy in the selection of patients with abdominal disease located to the spleen, liver, or the pelvic lymphatic chains. From January 1985 to January 1998, 94 previously untreated patients with biopsy-proven HD underwent clinical staging procedures consisting of history, physical examination, routine laboratory tests, chest radiography, total-body computed tomography scan, and bone marrow biopsy and were considered in stage I-IIA nonbulky. In addition, all patients underwent bipedal lymphangiography, which was positive in 12 (12.8%). Of the 82 patients with negative lymphangiography, 9 (11%) showed disease below the diaphragm at laparoscopy with multiple random spleen and liver biopsies. Of the remaining 73 patients, 32 were male and 41 were female with a median age of 29 years (range: 14–72 years).