28.06.2014 Views

Modern - Blog Science Connections

Modern - Blog Science Connections

Modern - Blog Science Connections

SHOW MORE
SHOW LESS

Create successful ePaper yourself

Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.

10 9.,0 MBKCC .. .,4<br />

B<br />

prot:oool<br />

1'1<br />

E<br />

--<br />

I 6<br />

~<br />

I<br />

l5<br />

4<br />

> 6<br />

0<br />

"<br />

bl •• t.<br />

3<br />

1<br />

1 e 3 4 15<br />

Fig. 1. Treatment-induced blast cell reduction<br />

in the bone marrow during induction<br />

therapy in five patients with<br />

ANLL. Open and solid stars represent<br />

cytoreduction rates in one patient who<br />

received two identical courses of the<br />

induction regimen<br />

4 weeks after completion of the first induction<br />

course. In one patient leukemic cell mass in the<br />

bm was only reduced by 1.4 10glO during<br />

induction therapy and posttreatment bm examination<br />

still showed 60% leukemie blasts.<br />

A second course of the identical regimen<br />

resulted in a similar cytoreduction of 1.7 10glO<br />

and 40 % blasts were found on posttreatment<br />

bm examination. The cytoreduction rates of<br />

this patient are represented by the two upper<br />

curves in Fig. 1.<br />

11. High Dose TdR<br />

For three of the four patients cell kill rates of<br />

0.17, 0.13, and 0.13 10glO per day were<br />

measured and all three achieved bm aplasia as<br />

documented by bm biopsy. The one patient<br />

who was treated over aperiod of 28 days<br />

achieved a total reduction in the leukemic bm<br />

cell mass of 3.6 10glO and went into eR. The<br />

fourth patient did not respond to TdR as<br />

judged by morphologie examination of bm<br />

aspirates and biopsies, and a total blast cell<br />

reduction of only 0.9 10glO (0.05 10glO/d) was<br />

found after 25 days of TdR therapy.<br />

D. Discussion<br />

Quantitation of chemotherapy-induced cytoreduction<br />

by monitoring the absolute number<br />

of leukemic cells per mm 3 bm provides a new<br />

quantitative determinant to evaluate treatment<br />

efficacy in acute leukemia. This parameter<br />

complements and facilitates clinical trials<br />

with new drugs such as high dose TdR, as the<br />

sensitivity of leukemic cells to the applied<br />

therapy is quantifiable in vivo and after short<br />

periods of drug exposure, which allows one to<br />

detect response or nonresponse at an early<br />

stage of treatment.<br />

For induction therapy of ANLL quantitation<br />

of therapeutic response not only permits<br />

74

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!