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Conrad Notes
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TOTAL THERAPY OF ACUTE MYELOID LEUKEMIA (AML)
R. Powles, MD, Royal Marsden National Health Service Trust, Sutton, UK, presented results on treating 52 consecutive newly diagnosed primary AML patients at a single center. The program consists of chemotherapy cycling followed by bone marrow transplant (BMT). Forty (77%) of the patients attained CR (complete remission) and 25 of 40 (63%) were alive up to 7 years later. Please see the US package inserts on cytarabine (Cytosar-U®) and idarubicin (Idamycin®).

Introduction A total therapy program at a single center may be a better way for testing intensive treatment protocols derived from multicenter, well-controlled trials. Powles reported on the use of this scheme in 195 newly diagnosed unselected myeloma patients (Bone Marrow Transplant 1997;20:435-443). The results of such assessment could help health providers judge the knowledge gained from well-controlled clinical research trials before application under less stringent conditions.

AML study patients Fifty-two consecutive newly diagnosed AML patients seen at a single medical center entered this study between April 1990 and August 1994. The patients ranged in age from 13 to 53 years (median,33.5). Karyotyping of 50 of 52 patients showed a favorable risk in 19 and unfavorable risk in 31.

Treatment protocol Total therapy began with inpatient induction using idarubicin (IDA) infused at 5 mg/msq plus cytarabine (CYTO) at 2 g/msq and high dose (100 mg/msq) VP-16 in 46 patients. The remaining six patients received mitoxantrone as a substitute for IDA.

Consolidation 1 consisted of one outpatient cycle of three blocks of CYTO (60 mg/msq) subcutaneously and 80 mg thioguanine orally. This was followed by an inpatient cycle of 100 mg/msq amsacrine, 200 mg/msq CYTO, and 100 mg/msq VP-16 (etoposide) daily for 5 days as Consolidation 2.

Allogeneic BMT using matched sibling allograft or unpurged autograft represents the last step in Powles' total therapy for primary AML. The dose for total body irradiation was 1050 cGy.

Clinical results of total therapy Forty of 51 (78%) evaluable patients achieved CR. None of the failures survived after intensive salvage therapy including allogeneic BMT. Overall survival at 35 to 86 mo posttreatment was 48%.

A favorable karyotype predisposed 18 of 19 (95%) patients to CR contrasted with 18 of 28 (64%) with other karyotypes (p=0.03). Comparison of survival rates of both groups (12/19 vs 10/28) showed borderline significance (p=0.08).

Investigator conclusions The effectiveness of therapy may be judged best by studying consecutive patients treated sequentially in one center. A program integrating chemotherapy and BMT is needed in adult AML. Reduction of total body irradiation to 950 cGy may improve the safety of allogeneic BMT and additional high-dose CYTO may reduce relapse after autografting.

Conrad comments Powles' myeloma and AML studies help fulfill the need for "real world" evaluation of regimens derived from well-controlled clinical trials. The UK National Health Service support made the current study possible in an effort to provide better patient care in a cost-effective manner. Perhaps other countries should allocate research funds similarly. Please see the related report on Hill's presentation in this issue of Conrad Notes.

For professional correspondence, please contact Dr. Powles by Fax at: 44 181 770 7313 or E-mail at: leukaemia@clara.net

Eugene A. Conrad

Presented at The American Society of Hematology (ASH) Meeting, December 5-9, 1997
Copyright © 1998 Conrad Group, Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / February 1998
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