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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2730-2741
Philadelphia Chromosome-Positive (Ph+) Childhood Acute
Lymphoblastic Leukemia: Good Initial Steroid Response Allows Early
Prediction of a Favorable Treatment Outcome
Martin Schrappe,
Maurizio Aricò,
Jochen Harbott,
Andrea Biondi,
Martin Zimmermann,
Valentino Conter,
Alfred Reiter,
Maria G. Valsecchi,
Helmut Gadner,
Giuseppe Basso,
Claus R. Bartram,
Fritz Lampert,
Hansjörg Riehm, and
Giuseppe Masera for the
German-Austrian-Swiss BFM Study Group and the Associazione Italiana
di Ematologia ed Oncologia Pediatrica (AIEOP)
From the Department of Pediatric Hematology and Oncology,
Medizinische Hochschule Hannover, Hannover, Germany; the Clinica
Pediatrica, Università di Pavia, Pavia, Italy; the Oncogenetic
Laboratory, University Children's Hospital, Gie en, Germany; the
Clinica Pediatrica, Ospedale S. Gerardo and the Institute of Biometry
and Statistics, Università di Milano, Italy; St Anna
Kinderspital, Wien, Austria; the Clinica Pediatrica, Università
di Torino, Torino, Italy; and the Institute of Human Genetics,
University of Heidelberg, Heidelberg, Germany.
Among 4,760 acute lymphoblastic leukemia (ALL) patients
enrolled from 1986 to 1995 in two subsequent trials of the BFM and AIEOP study group, 61 patients were found to have Philadelphia chromosome-positive (Ph+) ALL. These patients were
analyzed for presenting features and treatment outcome to identify
specific prognostic factors. Treatment stratification was based on
initial cell mass and early response as determined by blast count in
peripheral blood after a 7-day induction prephase with prednisone and
one dose of intrathecal methotrexate on day 1. All patients were
treated by similar intensive Berlin-Frankfurt-Münster (BFM)
protocols. The median age of Ph+ patients was 7.5 years,
the median white blood cell count (WBC) was 75 × 109/L,
77% of patients had common ALL, and 29% coexpressed myeloid markers.
After a median observation time of 4.2 years, 29 of 61 patients are
alive (survival probability [pSUR] at 4 years, 0.49; standard error
[SE], 0.06), and 24 of 61 are in first complete remission (CR1;
probability of event-free survival [pEFS] at 4 years, 0.38; SE,
0.06). Twenty (35%) of 57 evaluable patients had  1,000 leukemic
blasts per microliter of blood on day 8 of induction (defined as
prednisone-poor-response [PPR]). These patients were older (10.0 v 6.88 years; P = .02) and had a higher WBC (144 v 29 × 109/L; P = .0016) as compared
with patients with prednisone good response (PGR; <1,000 blasts/µL
at day 8). Only 2 of 20 patients (10%) with PPR remained in CR1 and
alive: 6 patients with PPR did not survive after allogeneic bone marrow
transplantation (BMT) due to recurring disease (n = 3) and toxicity
(n = 3), and 12 nontransplanted patients died due to progression
(n = 5) or relapse (n = 7). In contrast, 26 (70%) of the
37 patients with PGR are alive. Of 18 patients transplanted by
allo-BMT, 1 relapsed (now in CR2) and 4 died after BMT. Among the 19 patients with PGR treated by chemotherapy alone, 8 remained in CR1 and
11 relapsed, of which 4 are in CR2 or CR3. The prednisone response
emerged as the only independent prognostic factor for survival in Cox
regression analysis. Thus, two thirds of Ph+ childhood
ALL cases can be identified early by PGR, which, when treated with
intensive BFM chemotherapy, with or without BMT, have a significantly
lower risk of treatment failure. With a median continuous complete
remission (CCR) time of 4.1 years, pEFS for PGR is 0.55 (SE, 0.08) compared with 0.10 (SE, 0.07) in patients with PPR
(P = .0001). PGR is also an indicator for treatment
responsiveness and durable second remission after relapse, which in
turn may provide a second chance for BMT.
© 1998 by The American Society of Hematology.
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