Hematologic Oncology

Chronic myelogenous leukemia (CML) is an intriguing disease for reasons that point to important biological differences between this and other types of leukemia:

Individualizing the dosage of cancer chemotherapy can increase survival rates for children with acute lymphoblastic leukemia (ALL) without causing excessive toxicity, according to a recent study published in The New England Journal of Medicine.

SAN DIEGO-Up to 80% of newly diagnosed elderly acute myelogenous leukemia (AML) patients overexpress P-glycoprotein (P-gp), leading to multidrug resistance and a poor prognosis, said Dr. P. Sonneveld, University Hospital, Rotterdam, in a presentation at the American Society of Hematology (ASH) annual meeting.

ASH-Patients with chronic myelogenous leukemia (CML) who are eligible for transplant but lack a matched sibling donor should begin their search for an unrelated donor as soon as possible after diagnosis, A. James Morton, MD, said at the plenary session of the annual meeting of the American Society of Hematology (ASH) in San Diego.

Drs. Enright and McGlave succinctly review the biology of chronic myelogenous leukemia (CML) and highlight the therapeutic role of allogeneic stem-cell transplantation. Two points, however, warrant further discussion. The first is that a regimen containing interferon-alfa (Intron A, Roferon-A) is optimal front-line therapy for the great majority of CML patients.[1] The second is that use of an interferon-alfa-based regimen prior to allogeneic stem-cell transplantation does not adversely affect post-transplant mortality, morbidity, or anti-CML efficacy.

ASCO--Treatment with an investigational immunoconjugate, CMA-676, safely induced remissions in some patients with refractory or relapsed acute myelogenous leukemia (AML), Eric L. Sievers, MD, said in his poster presentation of the preliminary results at the American Society of Clinical Oncology annual meeting.

ORLANDO--Final results of a phase III trial show that monotherapy with IDEC-C2B8, a new chimeric monoclonal antibody being developed by IDEC Pharmaceuticals and Genentech, pro-duces favorable response rates in patients with relapsed low-grade or follicular non-Hodgkin's lymphoma (NHL).

ORLANDO--Combination therapy utilizing interferon alfa-2b (Intron A) and cytarabine is associated with improved cytogenetic response and survival over interferon alone in patients with chronic myelogenous leukemia (CML), a French study, presented at the 38th Annual Meeting of the American Society of Hematology (ASH), has shown.

ORLANDO--A preparative regimen employing a radiolabeled monoclonal antibody (MoAb), coupled with busulfan (Myleran) and cyclophosphamide (Cytoxan, Neosar), yielded a low relapse rate in patients with acute myelogenous leukemia (AML) undergoing bone marrow transplantation (BMT) while in first remission.

Leukemia Society of America (LSA) scientist Dr. Brian Druker has described a drug that may be useful for combatting chronic myelogenous leukemia (CML). The new drug may be able to target leukemia cells, a much sought-after approach to cancer treatment.

Responding to the need for more efficacious and less toxic treatments for chronic myelogenous leukemia (CML), researchers at the University of Pennsylvania are exploring a novel form of gene therapy. By interfering with the transmission of a crucial message, they hope to prevent malignant cell growth without affecting normal hematopoietic cells.

Following unmodified allogeneic bone marrow transplantation (BMT), up to 60% of patients with chronic myelogenous leukemia (CML) will relapse. The management of relapsed CML has proven especially difficult, because cytotoxic drugs and interferon-alfa (Intron A, Roferon-A) seldom cure the disease, and a second bone marrow transplant is associated with high mortality.

WASHINGTON--In an update of its 1994 report, the Institute of Medicine (IOM), of the National Academy of Sciences, has confirmed its original findings of an association between herbicides used in the Vietnam War and various health problems, namely, soft tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, and chloracne.

BOSTON--Researchers at New England Deaconess Hospital are seeking patients with Hodgkin's disease, non-Hodgkin's lymphoma, acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML) for an FDA-sponsored study of a humanized anti-Tac (interleukin-2 receptor) monoclonal antibody. The phase Ib/II multidose trial will study tolerance, therapeutic efficacy, and biological efficacy.

SEATTLE--While about 65% of adults with newly diagnosed, acute myelogenous leukemia (AML) are able to achieve complete remission of their disease, this remission is often short-lived when conventional postremission regimens are used. However, new approaches to postremission therapy are proving beneficial to patients, Robert J. Mayer, MD, said at a symposium held in conjunction with the American Society of Hematology's 37th Annual Meeting.

I would like to take issue with Dr. Bruce Cheson's response to a reader's question on the role of high-dose chemotherapy/autologous bone marrow transplantation (ABMT) in patients with non-Hodgkin's lymphoma (Oncology News International, December, 1995, page 25).

The management of Hodgkin's disease presents the clinician with several separate opportunities to intervene effectively. Not only is it possible to treat newly diagnosed patients with the knowledge that the majority will be cured, but also one can approach relapse with cautious optimism. Unlike most human neoplasms, Hodgkin's disease can be regularly cured even after relapse has occurred. The article by Drs. Yuen and Horning reviews available data on the outcome of treatment of first relapse of Hodgkin's disease, and summarizes the evidence indicating that relapsed disease can still be cured.

In most patients with newly diagnosed Hodgkin's disease, initial therapy is curative. However, a small portion of patients treated with radiotherapy alone for limited favorable disease, and a larger percentage of patients treated with combination chemotherapy, with or without radiotherapy, for advanced-stage or unfavorable disease relapse after initial remission. Patients relapsing after radiotherapy alone should do as well with salvage combination chemotherapy as patients with advanced disease who have never received radiation. In patients who relapse after combination chemotherapy, retreatment with the same regimen or employment of a non-cross-resistant regimen offers high response rates among those with favorable characteristics.

Drs. Yuen and Horning provide an excellent, detailed review of the current status of salvage therapy for patients who have relapsed after initial treatment for Hodgkin's disease. The authors cover the various scenarios that confront the oncologist who manages patients with this illness. Most patients who present with early-stage Hodgkin's disease (stage IA and IIA) are still treated with primary radiation therapy, although there is an increasing trend toward combined-modality therapy in early-stage disease. As is mentioned in the article, despite excellent complete response rates with current treatment, there is still a substantial rate of relapse, which can be as high as 25%.

ROCKVILLE, Md--The Food and Drug Administration has approved a new indication for Roche Laboratories' Roferon-A (interferon alfa-2A recombinant). The agent, previously approved for use in treating hairy cell leukemia and AIDS-related Kaposi's sarcoma, is now also indicated for the treatment of chronic phase, Philadelphia chromosome positive chronic myelogenous leukemia (CML).

While it would seem obvious that dose intensity is an important determinant of treatment outcome in aggressive lymphomas, actually there are very few prospective data to support this hypothesis. Circumstantial evidence derived from retrospective analyses suggests that dose intensity is of clinical significance.

Gaynor and Fisher provide a literature review and analysis of the significance of dose intensity in determining treatment outcome in patients with intermediate-grade non-Hodgkin's lymphoma (NHL). Since most of the patients in the studies reviewed had diffuse large-cell lymphoma or its variants, that is the term that will be used in the remainder of this commentary. In their analysis, Gaynor and Fisher reach the conclusion that in the dose range tolerable without extraordinary supportive measures, increasing dose intensity has no demonstrable benefit.

The comprehensive review by Drs. Gaynor and Fischer details the historical and prospective data on conventional doxorubicin-based chemotherapy in advanced-stage intermediate grade lymphoma. However, it does not address the question of dose intensity in the era of growth-factor and stem-cell support. As the authors carefully document, modest increases in the dose intensity of conventional agents has translated into little objective gain in curative outcome. The pivotal Intergroup study [1] has emphasized the value of prospective compararative trials and has established CHOP (cyclophosphamide, doxorubicin HCl, Oncovin, and prednisone) as the gold standard of conventional chemotherapy.

SEATTLE-The FDA has granted Immunex Corporation marketing clearance for Leukine (sargramostim), yeast-derived GM-CSF, for use in older adult patients with acute myelogenous leukemia (AML) following high-dose induction chemotherapy.

ASCO LOS ANGELES--In a multicenter phase II study of mitogua-zone (MGBG) in relapsed or refractory AIDS-related non-Hodgkin's lymphoma (NHL), more than one quarter of patients responded to the drug, and all of the complete responders experienced an increase in their CD4 counts, Alexandra M. Levine, MD, reported at ASCO.