Hematologic Oncology

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.

WASHINGTON--The FDA's Biological Response Modifiers Advisory Committee unanimously recommended approval of Hoffmann-La Roche Inc.'s Roferon-A (interferon alfa-2a, recombinant) for the treatment of adult patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML). The interferon is currently approved for use in hairy cell leukemia and AIDS related Kaposi's sarcoma.

LOS ANGELES--The final report of the Parma study, presented at the American Society of Clinical Oncology meeting, confirms the superiority of dose intensification with autologous bone marrow transplantation (ABMT) over conventional chemotherapy in patients with relapsed diffuse non-Hodgkin's lymphoma (NHL).

SAN DIEGO, Calif--Researchers have demonstrated that in at least some patients with chronic myelogenous leukemia (CML), benign hematopoietic stem cell progenitors coexist in the marrow with malignant cells, creating the possibility that autologous bone marrow transplantation can be used to treat the disease, Phillip McGlave, MD, said at a conference sponsored by the University of California, San Diego Cancer Center and UCSD School of Medicine.

Ong and Larson provide an excellent review of acute lymphoblastic leukemia (ALL) in adults. They thoroughly discuss such basic issues as the diagnosis and classification of ALL, prognostic factors, and the principles of treatment. They also discuss specific problems that arise, such as the treatment of ALL in the elderly and in those with Philadelphia chromosome-positive ALL. In addition, the authors comment on areas that do not yet have fully defined roles in treatment, such as the detection of minimal residual disease and various methods of admin-istering high-dose chemotherapy supported by allogeneic or autologous progenitor cells obtained from blood or marrow. Their views, as expressed in this paper, are reasonable and supported by appropriate references. This review will therefore expand on and underline comments made by the authors in several areas.

Intensive remission chemotherapy followed by post-remission consolidation and maintenance therapies has achieved complete remission rates of 75% to 90% and 3-year survival rates of 25% to 50% in adults with acute lymphoblastic leukemia (ALL). These results, although promising, are still less favorable than those achieved in childhood ALL. However, various novel experimental and clinical approaches show promise for improving cure rates. Also, specific therapies directed at high-risk subgroups with ALL are beginning to emerge. Detection of specific chromosomal abnormalities at diagnosis identifies patients who are at risk of failing to achieve remission, as well as those who are likely to have short, intermediate, or prolonged disease-free intervals after successful remission induction. Such prognostic information may, ultimately, be used to assign risk categories and to individualize post-remission therapy. [ONCOLOGY 9(5):433-450, 1995]

Acute lymphoblastic leukemia (ALL) in adults is clearly a "different disease" than ALL in children-a fact that is well documented in the article by Ong and Larson. As they indicate, more than half of adult patients relapse despite modern therapy, most within the first 2 years. It should be pointed out, however, as is mentioned at the beginning of the article, that "modern" induction was defined by Cancer and Leukemia Group B study 7612--a study begun in 1976 [1]. Thus, induction therapy has not changed substantially in 20 years. The addition of consolidation therapy and prolonged maintenance therapy has resulted in modest increases in response duration, but despite many variations on current regimens, there has been little change in outcome during the past decade.

Today, we can cure a significant portion of people with aggressive non-Hodgkin's lymphomas. The cure rate at 5 years for all patients with advanced diffuse large-cell lymphoma is approximately 35%.

Primary CNS lymphoma is rising in incidence in both the AIDS and non-AIDS populations. It is a non-Hodgkin's lymphoma that usually presents as a brain tumor, but the leptomeninges, eyes, and spinal cord also are