Acute Leukemias - Republican Scientific Medical Library

a 12.3 · Subset-Specific Approaches 165
Fig. 12.1. Subtype-specific approach to ALL therapy. MTX, methotrexate;
AC, cytarabine; POMP, vincristine, prednisone, 6-mercaptopurine,
methotrexate; IT inj., intrathecal injections; MRD, minimal residual
disease; PCR, polymerase chain reaction. 1 Rituximab is added
ferent noncross-resistant agents in tandem and in doseand
schedule-intense regimens such as Hyper-CVAD
formed the basis of many contemporary programs with
significant improvement in outcome [1, 22, 23]. Complete
remissions were attained in > 80% of patients; 2year
DFS rates increased to 60–80%. Relapses are rare
after the first year in remission. Intensive early prophylactic
intrathecal therapy (with or without cranial irradiation),
in addition to intensive systemic methotrexate
and ara-C, significantly reduced the CNS relapse rate.
In the modified hyper-CVAD program by Thomas,
et al., induction courses were administered in the laminar
airflow room for patients over age 60 years and rituximab
was added for high expression of CD20, which
is virtually ubiquitous in mature B ALL [24]. Thirty-one
human immunodeficiency virus (HIV)-negative patients
with either mature B ALL or Burkitt lymphoma
were treated. Median age was 46 years (range 17 to
77 years). A total of eight courses were planned with
two IT treatments accompanying each course for a total
of 16 IT treatments. Of 23 evaluable patients, the CR rate
was 91%. All nine patients over age 60 achieved a complete
remission. No induction deaths occurred. Among
17 patients who were followed for at least 1 year, no one
relapsed. Compared to a historical control population of
if CD-positive. 2 mediastinal irradiation is performed if bulky mediastinal
mass/adenopathy existed at diagnosis. 3 Imatinib, dasatinib,
nilotinib
48 patients with mature B ALL who were treated with
hyper-CVAD without addition of rituximab, response
rates (regardless of age) and 2-year survival rates were
superior with the modified hyper-CVAD approach.
Treatment of patients with mature B ALL associated
with the acquired immunodeficiency syndrome (AIDS)
or HIV remains challenging. Cortes, et al. reported the
hyper-CVAD experience in 13 patients [25]. Median
age was 43 years (range 32 to 55 years). Nine of the patients
received concomitant highly active antiretroviral
therapy (HAART). Nine patients were diagnosed with
HIV at diagnosis, whereas the remaining four patients
had a history of known HIV infection for a median of
37 months prior to the diagnosis of the leukemia/lymphoma.
Median absolute CD4 count was 77 cells/lL
(range 9 to 544 cell/ L) with only one patient maintaining
CD4 counts > 200 cells/lL. CR rate was 92%. Median
time of survival was 12 months and 48% of patients
were still alive at 2 years. Therapy with HAART is an
essential component of therapy for mature B ALL. Of
seven patients who received HAART from the start of
therapy, six were still alive and in CR after a median
of 29 months, whereas none of the four patients who
didn’t receive HAART survived. Toxicities were comparable
to that of non-HIV patients with mature B ALL.