Hematologic Oncology

High-dose therapy with hematopoietic progenitor-cell transplantation plays a key role in the treatment of Hodgkin’s disease and the non-Hodgkin’s lymphomas. First and foremost, transplantation is used as a salvage treatment for those who relapse or do not achieve a complete remission with first-line chemotherapy. Carefully selected patients with poor prognostic features may benefit from the incorporation of high-dose therapy and transplant into their initial treatment programs. Despite a myriad of trials, many pivotal questions regarding the appropriate application of high-dose therapy with transplantation to the lymphoid malignancies remain unsettled, including the role of allogeneic transplantation and the optimal timing of transplant for patients with poor prognostic indicators. Phase III studies are required to address these issues; these trials will demand the active commitment of concerned transplanters and referring hematologists and oncologists. Although autologous transplantation has been the preferred approach for the majority of patient subgroups, new approaches to allogeneic transplantation that have diminished toxicity may pave the way for a greater role for allogeneic grafting in the lymphoid diseases. [ONCOLOGY 13(12):1635-1645, 1999]

Data published in a recent issue of Blood suggest that valspodar (Amdray), a multidrug resistance modulator being developed by Novartis Pharmaceuticals Corporation, may show promise in treating certain patients with acute myelogenous leukemia

The combination of fludarabine and mitoxantrone (FM) has been shown to be an effective regimen for indolent lymphoma (J

MIAMI BEACH-Long-term follow-up of 23 patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in first complete remission showed a relatively low relapse rate at 3 years when treated with allogeneic bone marrow transplant from HLA-matched siblings, D.S. Snyder, MD, reported at the American Society of Hematology (ASH) annual meeting.

TUCSON-Cyclosporine (Sandimmune) significantly reduces resistance to daunorubicin (Cerubidine), prolongs the duration of remission, and improves overall survival of patients with high-risk acute myelogenous leukemia (AML), Alan F. List, MD, of the University of Arizona, said at the ASH meeting. Dr. List’s observations were based on a randomized trial conducted with the Southwest Oncology Group.

SEATTLE-Preliminary phase II data show that CMA-676, an engineered human anti-CD33 antibody linked to calicheamicin, a potent cytotoxic agent, produced an objective response in 10 of 23 patients (43%) with acute myelogenous leukemia in first relapse after initial chemotherapy. Six responders went on to allogeneic bone marrow transplant.

CHICAGO-A cost analysis of the use of G-CSF (Neupogen) in elderly patients undergoing intensive chemotherapy for acute myelogenous leukemia (AML) showed the agent to be almost cost neutral, Tammy J. Stinson, MS, said at a poster session of the American Society of Hematology annual meeting.

GOTEBORG, Sweden-A postconsolidation regimen of low-dose interleukin-2 (IL-2) and the investigational agent histamine dihydrochloride (Maxamine) appears to increase leukemia-free survival in acute myelogenous leukemia (AML) patients in remission, Bo I. Nilsson, MD, PhD, reported at an ASH poster session.

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that follows a characteristic clinical course in which a chronic phase of variable duration precedes an accelerated, and ultimately blastic, phase,

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).

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).