Acute Leukemias - Republican Scientific Medical Library

a 4.7 · Relapsed and Refractory Acute Promyelocytic Leukemia 69
Fig. 4.5. Outcome of the 122 APL patients in second hematological
complete remission according to postremission therapy. (A) Relapse-free
survival; (B) event-free survival; (C) overall survival [127].
studies demonstrate that patients with negative PCR
after achieving CR2 will fare well with autologous HSCT
and patients with positive PCR should not routinely be
offered an autologous HSCT.
4.7.5 Gemtuzumab Ozogamicin in Relapsed
Acute Promyelocytic Leukemia
Gemtuzumab ozogamicin offers a highly attractive
approach for treatment of APL for several reasons.
Firstly, compared to other AML subtypes, CD33 antigen
is detectable in virtually all cells with a highly homogeneous
expression pattern [129, 130]. Secondly, P-gp, a
mediator of MDR which acts as an efflux pump to extrude
chemotherapy, is minimally expressed on APL
blasts, which accounts for the striking sensitivity of
APL to anti-CD33 strategies [131]. Finally, calicheamicin
is a potent intercalator, similar to anthracyclines, which
are known to be highly effective in APL [132].
GO monotherapy in molecularly relapsed APL has
been well tolerated and is effective [118, 133]. Lo Cocco
and colleagues [118] demonstrated this in 16 such patients.
All patients were treated with two doses of GO
(6 mg/m 2 ), and a third dose was given to patients who
tested negative for PML-RARa fusion transcript. Molecular
response was obtained in nine (91%) of 11 patients
after two doses and in 13 (100%) of 13 patients after the
third dose. Of the three remaining patients, one patient
developed hepatic toxicity after a single dose of GO and
therefore received no further therapy, and remaining
two patients progressed while on treatment. Quantitative
RT-PCR demonstrated that patients who responded
had a dramatic decline (at least 2 logs) of the PML-
RARa transcript following first GO dose. Of 14 responders,
seven remained in sustained molecular remission
for a median of 15 months (range, 7 to 31 months) while
seven relapsed at 3–15 months later. GO was readministered
in two patients in relapse, and both achieved a
molecular remission. Since a high proportion of patients
relapsed, the authors suggested that patients
should be given further treatment (consolidation/maintenance)
after achieving molecular remission to improve
long-term outcome.