An unusual cause of adrenal insufficiency with elevation of 17-hydroxyprogesterone: case report.

BACKGROUND: We present an intriguing case of primary adrenal lymphoma, with associated primary adrenal insufficiency (PAI), in a patient presenting a transitory partial 21-hydroxylase deficiency during the active phase of the adrenal disease. CASE PRESENTATION: An 85-years old woman was referred because of worsening asthenia, lumbar pain, generalized myalgia and arthralgia. During investigations a computed tomography (CT) scan evidenced two large bilateral adrenal masses, highly suspicious for primary adrenal tumor. The hormonal assessment revealed very low levels of morning plasma cortisol and 24-h urinary cortisol, elevated ACTH levels with low plasma concentration of aldosterone, pointing to the diagnosis of PAI. After diagnosis of PAI our patient started glucocorticoid and mineralcorticoid replacement therapy with clinical benefit. In order to further characterize the adrenal lesions, adrenal biopsy, was performed. The histology revealed a high grade non-Hodgkin lymphoma with an immunophenotype consistent with intermediate aspects between diffuse large B-cell and Burkitt lymphoma, with a high proliferation index (KI-67 > 90%). The patient received chemotherapy with epirubicin, vincristine, cyclophosphamide, and rituximab, associated with methylprednisolone that resulted in a complete clinical and radiological remission within one year. After 2 years from the diagnosis and a total of 6 cycles of rituximab, the patient was in good clinical condition and was taking only the replacement therapy for PAI. The patient initially presented also a slight increase of 17-hydroxyprogesterone (17-OHP) for age that normalize after resolution of lymphoproliferative disease. CONCLUSIONS: In the presence of bilateral adrenal disease and/or in the presence of signs and symptoms of PAI clinicians must exclude the presence of PAL. The evidence of elevated ACTH-stimulated 17-OHP levels also in patients with other adrenal masses, together with the detection of elevated basal 17-OHP levels in our patient make it more plausible, in our view, an effect of the lesion on the "healthy" adrenal tissue residue than a direct secretory activity by the adrenal tumor.

Safety and efficacy of (90) yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients. An Italian cooperative study.

(90) Yttrium ((90) Y)-Ibritumomab-Tiuxetan combines the targeting advantage of a monoclonal antibody with the radiosensitivity of Follicular Lymphoma (FL). Previous studies showed that 90Y-IT is safe and effective in relapsed/refractory indolent FL, irrespective of prior treatment with rituximab. This multicentre trial aimed to evaluate the safety and the efficacy of "upfront" single-agent ((90) Y)-Ibritumomab-Tiuxetan in advanced-stage FL. The primary objective was the incidence of responses in terms of complete (CR) and partial remission (PR). Fifty patients with stage II "bulky", III or IV FL received a single treatment course with ((90) Y)-Ibritumomab-Tiuxetan as initial therapy. The median age was 60 years. Bone marrow involvement (<25%) was observed in 24 patients (48%) and 7 (14%) had an elevated lactate dehydrogenase level. The overall response (ORR) and CR rates were 94% and 86%, respectively with a median follow-up of 38·8 months. The median progression-free survival (PFS) was not reached, whereas the 3-year estimated PFS and overall survival (OS) rate was 63·4% and 90%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 30% and 26% of patients respectively; none experienced grade 3/4 non-haematological toxicity. No cases of secondary haematological malignancies were observed. ((90) Y)-Ibritumomab-Tiuxetan was demonstrated to be highly effective and safe as first-line treatment for advanced-stage FL.

Tandem autologous-reduced intensity allogeneic stem cell transplantation in high-risk relapsed Hodgkin lymphoma: a retrospective study of the Lymphoma Working Party-EBMT.

Autologous hematopoietic stem cell transplantation (ASCT) is curative for a proportion of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). However, there is a small group of patients with high-risk of relapse after ASCT that might benefit from other approaches. We conducted a retrospective analysis on 126 patients treated with tandem ASCT-reduced intensity conditioning (RIC)-allogeneic-SCT and reported to the EBMT registry to analyze the efficacy and safety of this approach. Patients were included if they had received an ASCT followed by a planned RIC-SCT in <6 months without relapse between the procedures. The median time between diagnosis and ASCT was 16 months (2-174). The median number of lines prior to ASCT was two (33% of the patients received >3 lines). Forty-one percent were transplanted with active disease. The median follow-up was 44 months (6-130). Three-year-progression-free survival (PFS), overall survival (OS), incidence of relapse (IR), and non-relapse mortality (NRM) after the tandem were 53% (45-64), 73% (65-81), 34% (24-42), and 13% (8-21), respectively. This is the largest series analyzing the efficacy and safety of a tandem approach in R/R HL. The low NRM and IR with promising PFS and OS suggest that this might be an effective procedure for a high-risk population.

Reduced intensity conditioning for allograft after cytoreductive autograft in metastatic breast cancer.

The benefits of allografting noted in some malignant diseases might be safely extended to metastatic breast cancer by a combination of cytoreduction with high-dose chemotherapy (HDT) and autologous stem-cell transplant (ASCT) with graft-versus-tumour effect mediated by transplanted donor immune cells with nonmyeloablative allografting (reduced intensity conditioning transplantation, RICT). 17 patients with heavily pretreated disease were given tandem transplants. 13 patients sustained donor engraftment. Three had partial remission after HDT and ASCT and complete remission after RICT; they achieved full chimerism and all developed graft-versus-host disease (GVHD) before regression of cancer. Another patient did not respond to HDT and ASCT but had partial remission after RICT, giving an overall response rate of 24%. Five patients had grade II or higher acute GVHD and five had extensive chronic GVHD. No non-relapse-related deaths occurred during the first 100 days. Five patients (29%) were alive 90-2160 days (median 1320) after RICT. This two-step approach is feasible in patients with metastatic breast cancer.

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.