Aggressive non-Hodgkin's lymphoma mimicking unilateral transitional cell carcinoma of renal pelvis. The risk of making a diagnostic mistake.

A 78-year-old Caucasian man was referred to our department because of an incidental unilateral mass involving the right renal sinus. As the patient showed no urological disease at flexible ureterorenoscopy, a subsequent percutaneous CT-targeted biopsy was mandatory, confirming an aggressive non-Hodgkin disease involving the renal pelvis that is, to the best of our knowledge, the second reported case in literature. A whole body FDG-PET excluded multiple expression of this disease, and the patient underwent a chemotherapeutic scheme resulting in a stable marked reduction in tumor volume. To the date, the available experience on the management and outcome of such cases is extremely lean. In this scenario, our case can contribute to shorten the time-to-diagnosis by reporting a complete images overview comprising abdominal CT scan, MRI and FDG-PET-CT, hence making this clinical entity easier presumable in clinical daily practice and offering a possible suggestion for an effective treatment.

Neurological syndrome after R-CHOP chemotherapy for a non-Hodgkin lymphoma: what is the diagnosis?

A 63-year-old man was admitted to our Oncology department for management of a follicular non-Hodgkin lymphoma, stage IV A FLIPI 5. The patient entered chemotherapy following the R-CHOP schedule, and a PET scan after three cycles showed partial remission. One week later he was admitted to our hospital after developing serious pain in his left arm resulting in an impaired function, right facial hemiplegia, and ophthalmoplegia. Neuroimaging studies and laboratory features were negative. Given his symptoms, we suspected Miller Fisher syndrome and the patient was administered high dose immunoglobulin, but showed no improvement. Finally, chemotherapy with methotrexate 3 g/mq was initiated, but his condition progressively worsened and the patient died 2 months later. We suggest that any patient with neurological symptoms who has received rituximab should undergo PCR analysis for all neurotropic viruses together with neurophysiological and neuroimaging studies.

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-Hodgkin's lymphomas (NHL) such as Burkitt's 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.

A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial.

BACKGROUND: The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC). METHODS: Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). High-ICE cycles were supported by transfusion with PBPCs that were collected after two cycles of treatment with epidoxorubicin at 150 mg/m(2), paclitaxel at 175 mg/m(2), and filgrastim. The primary outcome was 3-year survival. Comparisons between response rates and toxic effects within subgroups (limited or extensive disease, liver metastases or no liver metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, normal or abnormal lactate dehydrogenase levels) were also performed. RESULTS: Median relative dose intensity in the High-ICE arm was 293% (range = 174%-392%) of that in the Std-ICE arm. The 3-year survival rates were 18% (95% confidence interval [CI] = 10% to 29%) and 19% (95% CI = 11% to 30%) in the High-ICE and Std-ICE arms, respectively. No differences were observed between the High-ICE and Std-ICE arms in overall response (n = 54 [78%, 95% CI = 67% to 87%] and n = 48 [68%, 95% CI = 55% to 78%], respectively) or complete response (n = 27 [39%, 95% CI = 28% to 52%] and n = 24 [34%, 95% CI = 23% to 46%], respectively). Subgroup analyses showed no benefit for any outcome from High-ICE treatment. Hematologic toxicity was substantial in the Std-ICE arm (grade > or = 3 neutropenia, n = 49 [70%]; anemia, n = 17 [25%]; thrombopenia, n = 17 [25%]), and three patients (4%) died from toxicity. High-ICE treatment was predictably associated with severe myelosuppression, and five patients (8%) died from toxicity. CONCLUSIONS: The long-term outcome of SCLC was not improved by raising the dose intensity of ICE chemotherapy by threefold.

Primary subcutaneous B-cell lymphoma: case report and literature review.

Primary cutaneous B-cell lymphomas are defined as malignant B-cell proliferations presenting with cutaneous involvement alone and no evidence of extracutaneous manifestations when complete staging has been performed. It has been shown that the infiltrate in some cases could involve the underlying subcutaneous tissues, but primary localization in this compartment has been rarely reported. We describe here the case of a 53-year-old woman who noticed a nodular lesion on the left shoulder that rapidly enlarged in a few months. The histological and immunophenotypical features were compatible with a subcutaneous B-cell lymphoma. The tumoural mass was confined predominantly to the subcutaneous compartment, as confirmed by computed tomography. No other tumour localizations were found. Thus, primary B-cell lymphoma of the subcutis was diagnosed. We report a review of the literature indicating that B-cell lymphomas that are primarily localized to the subcutaneous tissues represent a very rare modality of presentation with a biological behaviour different from conventional cutaneous B-cell lymphoma.

Management of Frail and Not-Frail elderly cancer patients in a hospital-based geriatric oncology program.

PURPOSE: To evaluate management and outcome of patients >or=70 years admitted to our Medical Oncology ward and evaluated by Multidimensional Geriatric Assessment before treatment with standard or "elderly-friendly" chemotherapy regimens, a list of which was developed within our Geriatric Oncology Program based on published clinical trials and personal experience. PATIENTS AND METHODS: Charts of patients treated from January 2004 to January 2006 were reviewed for choice of treatment, tumor response, toxicities and survival. RESULTS: 117 patients (median age 75 years) were divided into Frail (F) (34.2%) and Not-Frail patients (NF: 33.3% Fit plus 32.5% Vulnerable). The two groups did not differ according to the use of "elderly-friendly"chemotherapy regimens (40% of F pts and 39% of NF pts), dose reductions >or=25% (37.5% vs. 31.2%) and grade 3-4 toxicities (52.5% vs. 58.4%). Early interruption of treatment due to toxicity or patient's refusal (42.5 vs. 15.6, p=0.001) and deaths within 30 days from last chemotherapy administration (22.5% vs. 3.9%, p=0.003) were significantly different. F patients showed clinical or radiological response in 21.2% of cases, and subjective improvement in 22.6%. After a median follow-up of 19 months, median survival of F patients (6.4 months) is shorter compared to NF group (16.9 months, p=0.012). CONCLUSIONS: The use of "elderly-friendly"chemotherapy regimens was limited to less than a half of cases. F patients may respond to chemotherapy but display higher rates of premature withdrawal and early deaths compared to NF patients, with a shorter survival. Clinical trials particularly aimed at frail patients are urgently needed.

Increasing chemotherapy in small-cell lung cancer: from dose intensity and density to megadoses.

The hypothesis that increasing cytotoxic dose intensity will improve cancer cure rates is compelling. Although supporting evidence for this hypothesis has accrued for several tumor types, including lymphomas, breast cancer, and testicular cancers, it remains unproven. Small-cell lung cancer is extremely chemo- and radiosensitive, with a response rate of 80% achieved routinely, but few patients are cured by chemoradiotherapy. In this setting, increased cytotoxic dose intensity might improve cure rates. The finding that response rates in small-cell lung cancer correlate with received cytotoxic dose intensity merely confirms that "less is worse" and "more is better." Within conventional ranges, dose intensity can be increased with the support of hematopoietic growth factors and/or by shortening treatments intervals; however, dose intensity could be increased by only 20%-30%, and a survival advantage has not been clearly demonstrated. Given its high chemosensitivity, small-cell lung cancer was one of the first malignancies deemed suitable for increasing dose intensity and even for the use of a megadose with the support of autologous bone marrow transplantation. Some interest is emerging again due to improvements in supportive care, such as the availability of hematopoietic growth factors and peripheral blood progenitor cells.

Occurrence of post-transplant lymphoproliferative disorders among over thousand adult recipients: any role for hepatitis C infection?

BACKGROUND: Post-transplant lymphoproliferative disorders represent an increasingly important complication of organ transplantation. Although the majority of the post-transplant lymphoproliferative disorder are etiologically related to Epstein-Barr virus infection other factors may play a role. Hepatitis C virus may induce clonal expansion of B-lymphocytes and has been associated with extrahepatic lymphoproliferative disorders. OBJECTIVES: In this study, we have evaluated: (i) the prevalence of post-transplant lymphoproliferative disorder; (ii) presence of Epstein-Barr virus in post-transplant lymphoproliferative disorder tissue; and (iii) the potential association between post-transplant lymphoproliferative disorder development and hepatitis C virus infection in a large cohort of adult solid organ transplant recipients. METHODS: The study involved 1011 liver, heart and kidney-transplanted patients. Different immunosuppression therapy was recorded from all patients, all were screened for hepatitis C virus infection. When post-transplant lymphoproliferative disorder developed, Epstein-Barr virus encoded RNA by in-situ hybridization and EBNA-1 and gp220 by polymerase chain reaction was assessed in tissue samples. RESULTS: The overall prevalence of post-transplant lymphoproliferative disorder was 1.4% (2.5% in heart, 0.9% in liver and 0.8% in kidney-transplanted patients) and significantly higher in hepatitis C virus positive than in hepatitis C virus negative patients (3.6 % vs 1.2 %; P=0.04). Epstein-Barr virus was present in 10 (77%) out of 13 tumors tested. Two out of three Epstein-Barr virus-negative post-transplant lymphoproliferative disorder developed in hepatitis C virus-positive patients. Thirteen out of 15 (86%) post-transplant lymphoproliferative disorder patients had undergone antithymocyte globulin/OKT3 induction therapy. CONCLUSIONS: Epstein-Barr virus, induction immunosuppression, rejection therapy and also hepatitis C virus infection may play a role in the multifactorial pathogenesis of post-transplant lymphoproliferative disorder.

Treatment of chemotherapy-induced oral mucositis with light-emitting diode.

OBJECTIVE: The aim of this study was to assess the clinical effectiveness of phototherapy with noncoherent light in the alleviation of chemotherapy-induced mucositis in patients with metastatic cancer. BACKGROUND DATA: Mucositis occurs in more than 40% of chemotherapy-treated patients, significantly reducing the quality of their lives. Many different interventions have been evaluated to reduce oral mucositis. Recently, good results have been achieved by phototherapy with photoradiation, a technique which has virtually no side effects. Some clinical results seem to indicate that also phototherapy through noncoherent light emissions which can be produced by less expensive light sources such as light-emitting diodes (LEDs) may be effective. However, until now, no studies have been available on this subject. METHODS: Twelve patients, aged from 34 to 82, selected on the basis of a diagnosis of chemotherapy-induced oral mucositis, were treated intra-orally through a noncoherent LED emission, wavelength 645 +/- 15 nm, 7.8 mW, fluence 0.99 J/cm(2), three times a day for 1 week. Mucositis was scored daily using the Daily Mucositis Index (DMI), a scale that evaluates the disease evolution through 16 different items. The primary end-point assessed was the time to recovery, from the start of LED treatment, compared to a nonrandomized control group of 12 patients with comparable stomatitis. RESULTS: The median healing time, expressed as the DMI decrease, was 1.7 (range 1-2.8) and, in seven LED-treated patients, was shorter than in the control group. The healing rate (measured as the ratio of the DMIs) increased from 117% to 164%. CONCLUSION: This pilot study shows that LED treatment is safe and capable of reducing the duration of chemotherapy-induced mucositis. This result needs to be confirmed in an adequate phase III study.

Long-term clinical outcome of AIDS-related Kaposi's sarcoma during highly active antiretroviral therapy.

The long-term impact of highly active antiretroviral therapy (HAART) in AIDS patients with Kaposi's sarcoma (KS) was evaluated in 22 consecutive, HAART-naïve KS patients attending a single Italian referral centre for HIV/AIDS. Clinical, virologic and immunologic responses to HAART were assessed at baseline and every three months during the follow-up. Peripheral blood mononuclear cell (PBMC)-associated human herpesvirus 8 (HHV-8) load was also evaluated by real-time PCR in 13 patients with durable clinical KS complete response (CR). In a median follow-up of 40 months (range 17-78), the KS overall clinical response rate was 91%: 18 complete and 2 partial responses were achieved, and two patients experienced disease progression. CR persisted in all 18 patients, including the 5 poor-risk KS patients in whom CR lasted for > 60 months, and was significantly linked to an increase in CD4+ cell counts and a drop in HIV-1-RNA copies. Compared to baseline levels, a decrease in PBMC HHV-8 load was observed at CR, and a significant further reduction was found at the end of follow-up. In this monocentric study, AIDS-KS patients treated with HAART showed high clinical response rate. Patients with CR showed a prolonged remission, lasting more than 5 years in a group of poor-risk patients, and a persistent reduction in circulating HHV-8-infected cells. These findings highlight that HAART deeply modifies the natural history of this tumour in AIDS patients, and that this long-lasting approach may be considered a first-line treatment for the majority of HIV-1-infected patients developing KS.

Treatments of AIDS-related Kaposi's sarcoma.

Although Kaposi's sarcoma (KS) has decreased in countries where the highly active antiretroviral therapy (HAART) regimen is available, however it remains, after non-Hodgkin's lymphomas, the most common malignancy in HIV+ patients. Advances in the treatment of AIDS-KS have been achieved, even though a gold standard therapy has not been yet defined. With the availability of HAART, a dramatic KS clinical response has been documented, making HAART essential in all patients. In case of aggressive and/or life threatening KS, more complex therapeutic schedules have to be taken into account, including chemotherapy and/or immunotherapy. Liposomal anthracyclines and paclitaxel have been approved by FDA as first line and second line mono-therapy, respectively. Interferon-alpha (INF-alpha) is the only immunomodulant agent to have shown a therapeutic effect. Among the new drugs, many antiangiogenetic agents have produced encouraging responses. Finally, the identification of the HHV-8 as a causative agent and new metalloproteinase inhibitors may offer promising targets for the KS treatment.

Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: a report from the non-Hodgkin's lymphoma co-operative study group.

The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL), Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36-70), received FLU/CY/MITO regimen (FLU 25 mg/m2 days 1-3, CY 300 mg/m2 days 1-3, Mito 10 mg/m2 day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87%: 46 patients achieved complete response (CR) (77%), 6 a partial response (10%) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2% and 45% respectively. Thirty-five patients (58%) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76%) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.

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 > or =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.

Nonmyeloablative allogeneic stem cell transplantation (NST) after truly nonmyeloablative and reduced intensity conditioning regimens.

Nonmyeloablative allogeneic stem cell transplantation (NST) has been explored to overcome transplant-related mortality (TRM). From the review of 39 published reports, 50% of the 1484 treated patients had NSTs with truly nonmyeloablative conditioning (NMC) and 417 patients (29%) received an unrelated donor transplant (UDT). Median age was 49 years (range 17-59). A median dose of 4.74 x 10(6) CD34+ per kg (range 1.7-7.5) was administered. Hematological recovery was rapid with all the regimens used. Sustained engraftment was obtained in 1267/1355 assessable patients (94%, range 67-100%). Complete donor chimerism was observed in 707/948 assessable patients (75%, range 22-100%). Both were higher after reduced intensity conditioning (RIC) than after NMC regimens. Reject was more frequent after UDT and NMC regimens. Grades II-IV and III-IV acute graft versus host disease (GVHD) occurred in 580/1400 (41%; range 7-72%) and 188/1093 (17%; range 0-29%) assessable patients, respectively; grades II-IV and III-IV acute GVHD were more frequent after UDT and RIC regimens, respectively. Chronic GVHD occurred in 407/1046 assessable patients (39%; range 0-79%) and extensive chronic GVHD in 166/835 patients (20%; range 0-69%); they were more frequent after RIC regimens and less frequent after UDT. Transplant-related mortality (TRM) rate of 20.6%, without differences between RIC and NMC regimens, was observed; TRM was higher with UDTs. The most frequent causes of TRM were acute or chronic GVHD after RIC regimens and infections after NMC regimens and UDTs. Indolent lymphoid malignancies and some solid tumors appear sensitive to the graft versus malignancy (GVM) effect. NSTs could guarantee relatively low TRM and toxicity in patients not eligible for conventional allogeneic transplantation and could represent a platform for successive specific immunotherapy.

Novel pharmacological therapies for the treatment of AIDS-related Kaposi's sarcoma.

Kaposi's sarcoma (KS) is the most common cancer associated with AIDS. KS aetiology and pathogenesis are still poorly defined and no definitive treatment has yet been identified. However, the introduction in 1996 of highly active antiretroviral therapy as a standard of care for those infected with HIV-1 determined a strong protection against the development of opportunistic infections, as well as a remission of pre-existing complications, including KS. Under highly active antiretroviral therapy, KS in particular has shown the highest clinical response rate reported to date among AIDS patients. Furthermore, recent insights into the pathogenetic mechanisms involved in KS development have provided new hope for a response and improved survival in patients with AIDS-related KS. This paper presents an overview of the current knowledge concerning pharmacological approaches to treating this disease. Newer treatments such as PEGylated liposomal anthracyclin, paclitaxel and pathogenesis-based strategies are also discussed.

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 Hodgkin's 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.