Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation.

In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n=43) or not receive (n=47) amifostine 910 mg/m(2) prior to melphalan 200 mg/m(2). Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness.

Prognostic features for response and survival in elderly patients with de novo acute myeloid leukemia treated with mitoxantrone and intermediate dose cytarabine.

Forty-three fit elderly patients with de novo acute myeloid leukemia (AML) received chemotherapy with mitoxantrone and intermediate dose cytarabine (MIDAC) in a phase II clinical trial conducted by the Australasian Leukaemia and Lymphoma Group. The main aim of the study was to evaluate the tolerability and efficacy of MIDAC in inducing durable remissions. While the chemotherapy was generally well tolerated, less than half the patients achieved complete remission (CR) after induction and many of those in CR could not receive planned consolidation cycles.

Infective mesenteric adenitis masquerading as relapsed non-Hodgkin's lymphoma.

Bulky mesenteric lymphadenopathy and B symptoms in a patient with a prior history of relapsed histologically aggressive non-Hodgkin's lymphoma would usually be attributed to recurrent disease. In the case described here, recurrent lymphadenopathy was found to be due to probable Yersinia infection, highlighting the need for rebiopsy of tissue in these circumstances wherever possible.

Optimal scheduling to reduce morbidity of involved field radiotherapy with transplantation for lymphomas: a prospective Australasian Leukaemia and Lymphoma Group Study.

This study evaluated delivery of involved field radiotherapy (IFRT) with transplantation for lymphomas timed to minimise toxicity. Patients transplanted for lymphoma had infradiaphragmatic disease irradiated pre-transplant and supradiaphragmatic disease post transplant. A total of 31 patients were studied, with a median follow-up duration of 4 years.

Interferon-alpha-2b and oral cytarabine ocfosfate for newly diagnosed chronic myeloid leukaemia.

Background: Treatment with interferon and subcutaneous cytarabine produces superior cytogenetic responses in chronic myeloid leukaemia (CML) than treatment with interferon alone, but at the expense of greater toxicity. Cytarabine ocfosfate (YNK01) is an oral precursor of cytarabine that may overcome some of the inconvenience and toxicities associated with subcutaneous cytarabine administration.

Patients And Methods: We studied the efficacy and tolerability of combination therapy with interferon-alpha-2b and YNK01 in patients with newly diagnosed, untreated CML.

The impact of conventional and high-dose therapy for lymphoma on fertility.

The impact of chemotherapy on gonadal function is an important issue for younger patients surviving lymphoma. This article reviews the effects on fertility of conventional and intensive-dose chemotherapy regimens with or without radiation therapy. In general, conventional dose regimens such as ABVD (doxorubicin/bleomycin/vinblastine/decarbazine) and CHOP21 (cyclophosphamide/doxorubicin/vincristine/prednisone) are not sterilizing, but data are limited on the effects of newer aggressive regimens such as BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone), CHOP14, and CHOP/etoposide.

A new model for predicting infectious complications during fludarabine-based combination chemotherapy among patients with indolent lymphoid malignancies.

Background: Fludarabine-containing combination chemotherapy regimens are increasingly used in the treatment of indolent lymphoid malignancies, with the associated risk of infection being the major toxicity. Predictors of infection during fludarabine-containing combination therapy are poorly defined and optimal strategies for infection prophylaxis are not known. The authors analyzed their experience with patients treated with the fludarabine-mitoxantrone (FM) or fludarabine-cyclophosphamide (FC) regimens to develop a predictive model for infections.

Graft-versus-lymphoma effects: clinical review, policy proposals, and immunobiology.

The indubitable existence of a graft-versus-lymphoma (GVL) effect is difficult to prove directly. This article reviews the difficulties in interpreting the current literature in this field and, with a number of caveats, argues for the existence of a clinically meaningful GVL effect in follicular, mantle cell, small lymphocytic, and Hodgkin lymphomas. The evidence, however, for a potent GVL effect in diffuse large-cell lymphoma and Burkitt lymphoma is not convincing.

Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation.

Cutaneous T-cell lymphomas (CTCL) are rare diseases that, in their advanced stages or in transformation, have a poor prognosis. Autologous stem cell transplantation (Au-SCT) after high-dose therapy has yielded disappointing results. Allogeneic transplantation (allo-SCT) provides the potential advantage of an immune-mediated graft-versus-lymphoma (GVL) effect.

Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations.

Mutations within the BCR-ABL kinase domain in imatinib-treated chronic myeloid leukemia (CML) are the main mechanism of acquired resistance. The early detection of mutations should provide clinical benefit by allowing early intervention. Quantitative polymerase chain reaction (RQ-PCR) results of BCR-ABL mRNA were correlated with mutation analysis in 214 patients treated with imatinib.

A pilot study of targeted itraconazole prophylaxis in patients with graft-versus-host disease at high risk of invasive mould infections following allogeneic stem cell transplantation.

Patients with severe graft-versus-host disease (GVHD) requiring intensive immunosuppression are at high risk of invasive mould infections (IMI). Prophylaxis with an active, oral antifungal agents with reliable absorption in this context is desirable. A total of 44 patients at high risk of post-engraftment IMI received itraconazole solution 2.

Risk factors for post-engraftment invasive aspergillosis in allogeneic stem cell transplantation.

The majority of invasive aspergillosis (IA) in allogeneic stem cell transplantation (SCT) occurs during the post-engraftment period. We used Cox proportional hazards regression to evaluate post-engraftment IA risk in a cohort of 217 allogeneic SCT recipients from 1991 to 1998. The aim was to quantify the effects of dose-intensity and duration of corticosteroids and other risk factors.

Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections.

ABSTRACT Treatment of invasive fungal infections is increasingly complex. Amphotericin B deoxycholate has long been the mainstay of treatment. However, there has been increasing recognition of both the propensity for nephro-toxicity in haematology, transplant and intensive care patients as well as its adverse impact on morbidity and mortality.

Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stem-cell transplantation.

Background: Existing data indicate that non-human leukocyte antigen (HLA) immunogenetic polymorphisms influence the risk of complications after allogeneic hemopoietic stem-cell transplantation. However, prior studies have been limited by small sample size and limited genotyping.

Methods: We examined 22 polymorphisms in 11 immunoregulatory genes including cytokines, mediators of apoptosis, and host-defense molecules by polymerase chain reaction using sequence-specific primers in 160 related myeloablative transplants.

Fatal anerobic bacteremia after hematopoietic stem cell transplant.

We describe 3 cases of fatal but clinically unsuspected anerobic bacteremia amongst hematopoietic stem cell transplant (HSCT) recipients treated empirically for fever and neutropenia with third or fourth generation cephalosporins. All patients had diarrhea but none had classical findings of neutropenic enterocolitis. HSCT recipients with fever, neutropenia and gastrointestinal tract symptoms such as abdominal pain or diarrhea or with septic shock despite broad spectrum antibiotics should receive an antimicrobial agent with anerobic activity.

A phase II study of escalated-dose docetaxel with granulocyte colony-stimulating factor support in patients with advanced breast cancer.

Purpose: Docetaxel is highly active in the treatment of patients with breast cancer. The principal dose-limiting toxicities of the 3-weekly regimen are neutropenia and febrile neutropenia. In a previous phase I dose-escalation study with granulocyte colony-stimulating factor (G-CSF) support, the recommended dose was determined to be docetaxel 160 mg/m(2) 3-weekly.

Cladribine followed by autologous stem-cell transplantation in progressive multiple sclerosis.

We studied the safety of autologous peripheral blood stem-cell transplantation (PBSCT) in four patients with progressive multiple sclerosis. Clinical and magnetic resonance imaging outcomes were secondary end-points. Cladribine administration preceded filgrastim-primed PBSC collection, aiming for lymphocyte depletion.

Primary adrenal lymphoma.

Primary adrenal lymphoma is a rare extranodal lymphoma with characteristic clinical features including a high incidence of bilateral involvement, predominantly diffuse large B-cell histology, and a low incidence of extra-adrenal disease at diagnosis. Patients are most commonly older men presenting with fever, lumbar pain, and/or symptoms of adrenal insufficiency. Prolonged disease-free survival appears uncommon, which may reflect a publication bias and/or the presence of additional adverse prognostic factors at diagnosis in most patients.

Esophageal perforation secondary to angio-invasive Candida glabrata following hemopoietic stem cell transplantation.

Esophageal perforation due to Candida glabrata is a rare entity. This organism is uncommonly recognized to be angio-invasive and cause gastrointestinal tract perforation. Herein, we describe a case of invasive C.

Pure red cell aplasia with the onset of graft versus host disease.

Pure red cell aplasia (PRCA) occurred in the fourth month after an ABO-compatible nonmyeloablative allograft coincident with the cessation of immunosuppression and the onset of limited chronic GVHD. No secondary causes could be identified. Erythropoiesis was restored promptly and durably with the resumption of immunosuppression.

Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin's lymphoma.

Pegfilgrastim is composed of the protein filgrastim to which a 20-kDa polyethylene glycol (PEG) is covalently bound at the N-terminal residue resulting in decreased renal clearance and increased plasma half-life compared with filgrastim. This open-label, randomized, phase 2 study compared two doses of single administration pegfilgrastim (60 and 100 microg/kg) with daily doses of filgrastim (5 microg/kg/day) or no cytokine treatment after standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy for non-Hodgkin's lymphoma in 50 elderly patients. The primary endpoint was the duration of grade 4 (severe) neutropenia (absolute neutrophil count < 0.

Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase.

We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points up to 18 months, P<0.0001.