Autologous Bone Marrow Transplantation - Blog Science Connections

60 ABMT in Acute Nonlymphocytic Leukemia
ctyopreservation are warranted. Preclinical studies have shown that rat
leukemia cells are eliminated from marrow suspensions by incubation ex vivo
with 4-hydroperoxycyclophosphamide (4-HC) (8), a congener of cyclophosphamide
and an active alkylating agent in aqueous solution (9). A phase 1 trial of
autologous transplantation with marrow treated with 4-HC in patients with
leukemia and lymphoma has demonstrated that hematopoietic repopulating
ability is not impaired after incubating marrow with up to 100 ug/m\ 4-HC (10).
In the study reported here, ABMT was carried out in 40 patients with ANLL in
second or third remission using marrows incubated with 60-100 UQ/ml 4-HC to
determine if ABMT with 4-HC-treated marrow can provide long-term diseasefree
survival. We also evaluated the toxicities of this regimen and the
hematologic engraftment parameters after infusion of 4-HC-treated marrow.
METHODS OF STUDY
Informed Consent
All protocols for marrow treatment and pretransplantation myeloablative
therapy were reviewed and approved by the Joint Committee on Clinical
Investigation of The Johns Hopkins Medical Institutions. Informed consent was
obtained from all patients and from the parents of patients who were children.
Patients
Forty consecutive patients (21 males and 19 females) were included in this
study. Median age was 30 years (range, 4-54 years). The diagnosis of ANLL was
confirmed in all patients by examination of bone marrow aspirates. Histologic
types of leukemia were classified according to guidelines of the French-
American-British (FAB) Cooperative Group (11). The patients had the following
FAB morphologic classifications: 17, M-|; 4, M 2
; 4, M 3
; 12, M 4
; and 3, M 5
. All
patients had had at least one hematologic relapse of leukemia and had received
intensive chemotherapy to induce initial and subsequent remissions. The
median duration of first remission was 15 months (range, 2-96 months). At the
time of marrow collection and transplantation, 30 patients were in second and
10 were in third complete hematologic remissions. Two patients had histories
of extramedullary leukemia: one patient in second remission had CNS
involvement at diagnosis, and one patient in third remission had both CNS and
testicular involvements at the time of first relapse. However, no patients had
active extramedullary leukemia at the time of marrow collection and transplantation.
Marrow Collection, Processing, and Infusion
The patients underwent marrow collection at a median of 2 months (range,
0.5-6 months) after attainment of second or third remission. Marrow was
aspirated from the posterior iliac crests according to previously published