MENARCHE IN A COHORT OF 188 LONG-TERM SURVIVORS OF ACUTE LYMPHOBLASTIC-LEUKEMIA

Objective: As more children survive acute lymphoblastic leukemia (ALL) , questions are raised regarding how the disease and its therapy affec t their pubertal development. Study design: The National Institute of Child Health and Human Development-National Cancer Institute-Children' s Cancer Group Leukemia Follow-Up Study used a historical cohort desig n to investigate menarche in 188 ALL survivors who were premenarchal a t diagnosis, aged at least 18 years, at least 2 years after diagnosis, alive, and in remission. Female siblings of ALL survivors (n = 215) s erved as control subjects. Results: Menarche occurred within the norma l age range in 92% of survivors and 96% of the control subjects (p = 0 .09). Early menarche occurred in four survivors (2%) and three control subjects (1%). Delayed, absent, or medically induced menarche was rep orted by 12 survivors (6%) and six control subjects (3%). Compared wit h the control subjects, survivors of ALL who received 1500 cGy cranial radiation before the age of 8 years had significantly earlier menarch e, relative hazard (RH) of 2.2 (95% confidence interval: 1.4, 3.4 [p = 0.0003]). Survivors receiving 2400 cGy of craniospinal radiation with or without abdominal radiation had significantly later menarche than the control subjects, RH 0.4 (95% confidence interval: 0.3, 0.7 [p = 0 .0002]). Conclusions: In this large cohort of ALL survivors, the risk of disordered menarche was low. However, younger subjects receiving 18 00 cCy cranial radiation and those receiving 2400 cCy below the diaphr agm required careful monitoring.