Consolidation therapy: what should be the standard of care?

Adults 18-60 years old with acute myelogenous leukemia (AML) should undergo some form of postremission therapy, however, how much and what kinds of postremission chemotherapy remain unclear. In contrast, for older patients more than one cycle of chemotherapy postremission does not appear justified except perhaps in those rare patients with favorable cytogenetics who are young enough to tolerate standard therapy and in whom there is still an option for cure. Routine postremission therapy is not justifiable for those with unfavorable cytogenetics.

Non-Hodgkin's lymphoma presenting as an endobronchial tumor: report of eight cases and literature review.

Non-Hodgkin's lymphoma (NHL) involving the endobronchial tree is uncommon, and the initial presentation of NHL as an endobronchial tumor is extremely rare. In a series of 441 patients with newly diagnosed non-Hodgkin's lymphoma over a 7-year period, we reviewed the clinical features of eight patients who presented with an endobronchial tumor. All patients had local pulmonary disease without extrathoracic involvement.

Indications for hematopoietic cell transplantation in acute leukemia.

Based on available data, all adults with AML under age 60 years with matched siblings should be considered for allogeneic transplantation in first remission, except for those with favorable risk cytogenetics and possibly those whose disease has normal cytogenetics and is FLT3/ITD negative and NPM1 positive. Patients with matched siblings not transplanted in first remission should be followed closely so that transplantation in early first relapse can be considered. Those without matched siblings should receive a MUD transplant in first CR if they have higher risk disease.

Recent developments in acute myelogenous leukemia therapy.

Recent progress has been made in several areas in the treatment of acute myelogenous leukemia (AML): prognostic factors, allogeneic bone marrow transplantation, and new and targeted therapies. Delineation and clarification of prognostic factors have led to improved risk determination, with research moving from cytogenetics to an examination of molecular markers. Trends in the area of allogeneic bone marrow transplantation include broad adoption of reduced-intensity conditioning despite the lack of prospective comparative studies.

In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993).

An international collaboration was set up to prospectively evaluate the role of allogeneic transplantation for adults with acute lymphoblastic leukemia (ALL) and compare autologous transplantation with standard chemotherapy. Patients received 2 phases of induction and, if in remission, were assigned to allogeneic transplantation if they had a compatible sibling donor. Other patients were randomized to chemotherapy for 2.

Gonadotropin-releasing hormone agonist decreases chemotherapy-induced gonadotoxicity and premature ovarian failure in young female patients with Hodgkin lymphoma.

Objective: To minimize the gonadotoxic effect of chemotherapy by the cotreatment with a GnRH agonistic analogue (GnRH-a).

Design: Prospective nonrandomized study with concurrent and historical controls.

Setting: University medical center.

How I treat acute lymphocytic leukemia in adults.

The treatment of newly diagnosed acute lymphocytic leukemia (ALL) in adults remains unsatisfactory. Not withstanding the outstanding progress in curing childhood ALL, only approximately one third of adults younger than 60 years can be cured, and the overall published survival curves have not changed significantly during the past 15 years. Recent therapeutic advances in allogeneic transplantation through the conduct of large collaborative studies, better understanding of the relevance of cytogenetics, improved molecular techniques for the detection of minimal residual disease, and clinical research into novel biologic and targeted therapies have all combined to offer potentially a better hope for an improved outcome in this disease.

Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers.

Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL).

Impact of cytogenetics on outcome of matched unrelated donor hematopoietic stem cell transplantation for acute myeloid leukemia in first or second complete remission.

We compared the treatment-related mortality, relapse rate, disease-free survival (DFS), and overall survival (OS) by cytogenetic risk group of 261 patients with acute myeloid leukemia in first complete remission (CR1) and 299 patients in CR2 in undergoing matched unrelated donor hematopoietic stem cell transplantation (HSCT). For patients in first CR, the DFS and OS at 5 years were similar for the favorable, intermediate, and unfavorable risk groups at 29% (95% confidence interval [CI], 8%-56%) and 30% (22%-38%); 27% (19%-39%) and 29% (8%-56%); and 30% (95% CI, 22%-38%) and 30% (95% CI, 20%-41%), respectively. For patients in second CR, the DFS and OS at 5 years were 42% (95% CI, 33%-52%) and 35% (95% CI, 28%-43%); 38% (95% CI, 23%-54%) and 45% (95% CI, 35%-55%); and 37% (95% CI, 30%-45%) and 36% (95% CI, 21%-53%), respectively.

Safe and efficacious allogeneic bone marrow transplantation for nonmalignant disorders using partial T cell depletion and no posttransplantation graft-versus-host-disease prophylaxis.

In an attempt to abrogate the deleterious effects of graft-versus-host disease (GVHD), allogeneic transplantation for nonmalignant diseases was performed using high-dose CD34-cell infusion, partial T cell depletion, and no posttransplantation GVHD prophylaxis. Between 1998 and 2004, 16 patients with matched related donors were treated. Median age was 1.

Differential gene expression patterns and interaction networks in BCR-ABL-positive and -negative adult acute lymphoblastic leukemias.

Purpose: To identify gene expression patterns and interaction networks related to BCR-ABL status and clinical outcome in adults with acute lymphoblastic leukemia (ALL).

Patients And Methods: DNA microarrays were used to profile a set of 54 adult ALL specimens from the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group E2993 trial (21 p185BCR-ABL-positive, 16 p210BCR-ABL-positive and 17 BCR-ABL-negative specimens).

Results: Using supervised and unsupervised analysis tools, we detected significant transcriptomic changes in BCR-ABL-positive versus -negative specimens, and assessed their validity in an independent cohort of 128 adult ALL specimens.

Alternative donor transplantation in acute myeloid leukemia: which source and when?

Purpose Of Review: Acute myeloid leukemia is a heterogeneous disease with a prognosis determined mostly by the leukemic karyotype. Allogeneic transplant in first remission is offered to patients with intermediate- and poor-risk cytogenetics. Only the minority of patients, however, have a matched sibling donor.

Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial.

Pretreatment cytogenetics is a known predictor of outcome in hematologic malignancies. However, its usefulness in adult acute lymphoblastic leukemia (ALL) is generally limited to the presence of the Philadelphia (Ph) chromosome because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1522 adult patients enrolled on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial.

Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study.

Most adults with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR) will relapse. We examined the outcome of 609 adults with recurring ALL, all of whom were previously treated on the Medical Research Council (MRC) UKALL12/ECOG2993 study, where the overall survival (OS) of newly diagnosed patients is 38% (95% confidence interval [CI]=36%-41%) at 5 years. By contrast, OS at 5 years after relapse was 7% (95% CI=4%-9%).

Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high-risk Hodgkin lymphoma with no impairment of outcome.

Therapy of Hodgkin disease (HD) is designed to prolong progression-free survival and minimize toxicity. The best regimen to achieve this has not yet been defined. A total of 108 patients with newly diagnosed HD and adverse prognostic factors were prospectively studied between 1999 and 2004.

Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial.

The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.

Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993.

Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with l-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy.

Is there a role for consolidation therapy pre-transplantation?

There is much confusion and uncertainty regarding the need for consolidation therapy before bone marrow transplantation. There are no prospective studies that have established clear guidelines and much of the information has been based on retrospective analyses of data obtained from the international bone marrow transplant registries. These data suggest that there may not be a role for consolidation therapy before an allogeneic transplantation.