Myelodysplastic Syndromes

ORLANDO - The thalidomide analog lenalidomide (CC-5013, Revlimid) significantly reduced the need for blood transfusions in patients with myelodysplastic syndrome (MDS) who had interstitial deletions in band 31 of the long "q" arm of chromosome 5, the most common cytogenetic abnormality in MDS, a multicenter phase II study has found. More than two-thirds of patients with 5q31 deletions achieved transfusion independence in response to the drug, and 44% had a complete cytogenetic response, Alan List, MD, reported at the American Society of Clinical Oncology 41st Annual Meeting (abstract 5).

Priming of leukemic cells with cytokines may enhance the efficacy of cell-cycle chemotherapy. In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS. A total of 80% of patients received all of the GM-CSF doses; 78% of patients received all of the cytosine arabinoside doses. Adverse events were minimal. No patient developed mucositis or alopecia. The most common adverse event was neutropenic fever, which was noted in 57% of patients. Twenty-one percent of patients remained neutropenic after treatment until death or relapse. Sixty-eight percent of patients reached an absolute neutrophil count of greater than 1,000 μL in a median of 33.5 days. Our data show an overall response rate of 52%, with a complete response rate of 39% and a partial response rate of 13%. Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.

SAN DIEGO, California-One in four Hodgkin’s disease (HD) patients has become a parent since participating in prospective trials of an experimental first-line regimen, known as Stanford V, designed to reduce toxicity from chemotherapy and radiotherapy.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

SAN DIEGO-There have been no reported cases of treatment-related myelodysplastic syndrome and acute myeloblastic leukemia (tMDS/tAML) in patients with low-grade non-Hodgkin’s lymphoma (NHL) treated initially with the Bexxar therapeutic regimen (tositumomab and iodine-131 tositumomab).

CHICAGO-Adjuvant therapy with epirubicin (Ellence) followed by cyclophosphamide, methotrexate, and 5-fluorouracil (ECMF) prolongs relapse-free survival and overall survival with only modest toxicity in patients with early-stage breast cancer and should replace upfront CMF as standard therapy in that setting, Christopher J. Poole, MD, said at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 13).

BETHESDA, Maryland-Members of the FDA’s Oncologic Drugs Advisory Committee (ODAC) gave a mixed review to Corixa’s Bexxar (tositumomab and iodine I-131-tositumomab), a radioactive-labeled monoclonal antibody intended to treat certain non-Hodgkin’s lymphoma (NHL) patients.

In the last 20 yearsof the past millennium,most clinical researchin leukemiawas directed towardimproving prognosisof acute leukemia andstudying the role ofstem cell transplantation(SCT), both autologousand allogeneic,in these diseases.The emergence of new treatments and therapeuticapproaches has dramatically changed the emphasisof clinical research in leukemia. The power ofeffective new agents to transform clinical research hasbeen illustrated by the emergence of the tyrosine kinaseinhibitor imatinib mesylate (Gleevec, STI-571) inchronic myeloid leukemia and monoclonal antibodiesin chronic lymphocytic leukemia (CLL).

SAN FRANCISCO-The investigationalfarnesyl transferase inhibitor(FTI), R115777 (tipifarmib,Zarnestra) causes robust clinical responsesin some patients withmyelodysplastic syndrome (MDS),but these responses are not correlatedwith the drug's ability to inhibitfarnesyl transferase, according to astudy presented at the 93rd AnnualMeeting of the American Associationfor Cancer Research (abstract 4959).

The bone marrow failure states, aplastic anemia and myelodysplastic syndrome, are characterized by reticulocytopenic anemia, with variable neutropenia and thrombocytopenia. The bone marrow biopsy is very hypocellular in aplastic anemia, but it is usually hypercellular in myelodysplastic syndrome.

LUGANO, Switzerland-In previously untreated, advanced Hodgkin’s disease, the ChIVPP/EVA regimen, though associated with risk of sterility, is highly effective with a low incidence of secondary leukemias, according to a recent analysis of two randomized studies.

NEW YORK-Adding the monoclonal antibody HuM195 to chemotherapy for advanced acute myeloid leukemia (AML) produced a trend toward better patient response rates than chemotherapy alone in a phase III trial (ASCO abstract 1042).

SAN FRANCISCO-The investigational farnesyl transferase inhibitor (FTI), R115777 (tipifarmib, Zarnestra) causes robust clinical responses in some patients with myelodysplastic syndrome (MDS), but these responses are not correlated with the drug’s ability to inhibit farnesyl transferase, according to a study presented at the 93rd Annual Meeting of the American Association for Cancer Research (abstract 4959).

LOS ANGELES-Myelodysplastic syndrome and aplastic anemia are both diseases of bone marrow failure and are characterized by reticulocytopenic anemia, with variable neutropenia and thrombocytopenia. Other than that, the two diseases are substantially different from each other. Tools for diagnosing and managing these two complex diseases were updated by Ronald L. Paquette, MD, associate professor of medicine at the University of California Medical Center in Los Angeles

The US Food and Drug Administration (FDA) has approved ibritumomab tiuxetan (Zevalin) for the treatment of relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL), including rituximab (Rituxan)-refractory disease.

Yttrium-90 ibritumomab tiuxetan (Zevalin) has been shown to be an effective and well-tolerated therapy for patients with relapsed B-cell non-Hodgkin’s lymphoma (NHL), with a response rate significantly higher than that seen with rituximab (Rituxan).

It is amazing how, over the past 5 years, the world of clinical research in the lymphoid malignancies has been totally redirected by one molecule called rituximab (Rituxan).

The third edition of the Color Atlas of Clinical Hematology, authored by Drs. A. Victor Hoffbrand and John E. Pettit, contains 19 chapters covering the entire spectrum of hematology, including normal hematopoiesis, benign and malignant

SAN FRANCISCO-Mature survival analyses from the North American Breast Intergroup Trial (INT-0100; SWOG-8814) confirm that chemotherapy plus tamoxifen (Nolvadex) produces better overall and disease-free survival than tamoxifen alone in postmenopausal women with node-positive, receptor-positive breast cancer.

A subcommittee of the Oncologic Drugs Advisory Committee (ODAC) recently spent a day discussing the similarities and differences between pediatric and adult hematologic malignancies. It was the second session in a series intended to advise the

GAITHERSBURG, Maryland-Animal studies of amifostine (Ethyol) are being used to explore optimal subcutaneous (SC) treatment and to refine approaches to dosing and scheduling of the radioprotectant. David R. Cassatt, PhD, of MedImmune, Inc., Gaithersburg, Maryland, described current preclinical work with amifostine.

SAN FRANCISCO-High-dose adjuvant chemotherapy with stem cell support provided no overall or disease-free survival benefit over standard chemotherapy in a randomized, multicenter Italian trial including 398 metastatic breast cancer patients.

ROCKVILLE, Md-Epoetin alfa, or recombinant human erythropoietin (Epogen, Procrit), reduces the need for red blood cell (RBC) transfusions among cancer patients with chemotherapy-induced anemia, a report prepared for the Agency for Healthcare Research and Quality (AHRQ) concludes. Overall, the report found that epoetin appears most efficacious when it is initiated as falling hemoglobin (Hb) levels near 10 g/dL.

Over the past 15 years, research into the health-related quality of life (HRQOL) of cancer patients has expanded dramatically. We have seen the development of a variety of instruments to assess both global HRQOL as well as cancer-specific symptoms. These instruments have been validated in a variety of populations. Many of the instruments have been translated into multiple languages. We have also seen the development of instruments to evaluate HRQOL in children and in adults with low literacy levels. We have learned how to integrate HRQOL questions into cancer clinical trials and how to facilitate the collection of QOL data from patients and their families. We are now beginning to evaluate interventions to maintain and enhance HRQOL among cancer patients and cancer survivors.

The second edition of Pediatric Hematolgy, edited by the text's original editors, John S. Lilleyman and Ian M. Hann, as well as a new editor, Victor S. Blanchette, completely updates and expands upon the first edition (published in 1992). The new edition grew from 15 to 40 chapters, with contributions by many of the most well-known investigators and clinicians in pediatric hematology in the world. The textbook will especially be of value to practicing clinicians, house staff, and students.

Transformation from indolent B-cell non-Hodgkin's lymphoma (NHL) to a more aggressive histology occurs frequently in the natural history of these diseases, and is generally associated with a poor prognosis. Histologic conversion occurs in 25%-80% of patients with follicular NHL, but is less frequently seen in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), reported in 3%-10% of patients. Between December 1982 and August 1997, 27 patients (14 male, 13 female) with a history of indolent B-cell NHL/CLL that had transformed to diffuse large B-cell lymphoma (DLCL) underwent autologous bone marrow transplantation (BMT). All patients were previously treated for indolent NHL/CLL with a median of threeprior therapies, and were similar with respect to whether transformation occurred early (< 18 months from diagnosis) or late.

GAITHERSBURG, Md-The Oncologic Drugs Advisory Committee (ODAC) has unanimously recommended the approval of Busulfex Injection (busulfan, Orphan Medical) in combination with other chemotherapeutic agents and/or radiation as a conditioning regimen prior to hematopoietic progenitor cell transplantation-but only in chronic myelogenous leukemia (CML).

PARIS--The development of valid, reliable yardsticks for measuring quality of life (QOL) is now making it possible for clinicians to advise patients about what they can realistically expect from a particular treatment, Jimmie Holland, MD, of Memorial Sloan-Kettering Cancer Center, said at the Eighth International Congress on Anti-Cancer Treatment (ICACT).

ASH-Topotecan (Hycamtin) given in combination with cytarabine (ara-C) produced a complete response rate of 63% in 35 patients with previously untreated, poor-prognosis myelodys-plastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), Miloslav Beran, MD, PhD, said at the American Society of Hematology annual meeting in San Diego.

PHILADELPHIA-The Huntsman Cancer Institute at the University of Utah is the newest member of the National Comprehensive Cancer Network (NCCN), bringing the number of member institutions to 16.