These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.

Sixty consecutive patients with untreated acute leukemia alternately received either ABO-matched or ABO-mismatched random-donor platelet transfusions prepared from pooled platelet concentrate stored for 1 to 3 days. Patients were assigned randomly to receive matched or mismatched platelets as their first transfusion, and the first four transfusions were analyzed. In 40 evaluable patients, there was no significant difference (paired t test) between the 10-minute posttransfusion corrected count increments (CCI) of the initial transfusions of matched and mismatched platelets. In contrast, the second matched transfusion was significantly better than the second mismatched transfusion. This effect of ABO compatibility was particularly pronounced in a subset of patients. Six patients in whom mismatched transfusions were consistently inferior to matched transfusions had either a significant increase in anti-A or -B isoagglutinin titers following the first transfusion or elevated titers before or at the conclusion of the study. Conversely, in five patients in whom there was no apparent effect of ABO mismatching, only one had an increase in isoagglutinin titer. Platelet survival was not altered as the ratio of 18-hour to 10-minute posttransfusion CCl was 0.6 for both matched and mismatched platelet transfusions. These data demonstrate that ABO compatibility can affect the results of random-donor platelet transfusions and that patients who experience poor increments from ABO-mismatched platelets may benefit from a trial of ABO-compatible platelets before the initiation of HLA-matched platelet transfusion.

Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras- positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.