Effectiveness of Protected Environment Rooms for AML and MDS

Leukemia Department policy has been to place patients age >/= 50 years with untreated AML or
high-risk MDS in the Protected Environment (PE) during the approximately 5 week period
needed to achieve CR. Comparisons between patients given initial induction therapy inside or
outside the PE have found that, after accounting for prognostic covariates such as age,
organ function, and sensitivity of the underlying disease to treatment, the PE is associated
with higher remission rates and longer survival (refs 1-2). These comparisons may have
suffered because the decision to treat in the PE was not made randomly.

Essentially, all the above patients received traditional chemotherapy. The lack of benefit
commensurate with this risk of death has led to the development of "less intense"
("targeted") therapies. Since, by definition, these treatments should produce less mortality
and morbidity than traditional therapies, it is not surprising that our prevailing practice
has become to treat even relatively old patients given targeted therapies outside the PE.

The rationale underlying this protocol is that it is not clear that the prevailing practice
is entirely satisfactory. Thus, within 6 weeks of beginning decitabine- or
azacitidine-containing therapies, 3 of the 42 patients treated outside the PE died and 4
others developed pneumonia or sepsis for a mortality and morbidity (M&M) rate of 17%( 7/42).
Within 6 weeks of beginning treatment, there were no induction deaths and 1 episode of
pneumonia among the 11 patients given decitabine- or azacitidine- containing therapies in
the PE for an M&M rate of 9%.

Since these comparisons are again confounded by the lack of randomization, the purpose of
this protocol is evaluate the effect of the PE by (adaptively) randomly assigning patients
age >/= 60 given targeted therapies between treatment inside or outside the PE.