Acute Leukemias - Republican Scientific Medical Library

184 Chapter 14 · Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Table 14.3. Outcomes after hematopoietic stem cell transplant
Ref. Author Years N EFS years
[94] Barrett, et al. 1978–1990 67 31% 2y
[101] Snyder, et al. 1984–1997 23 64% 3y
appear to have a significant effect on outcome, as the
higher risks of relapse in the related setting is offset
by problems with GVHD in the unrelated setting [41].
14.5 The Detection of Minimal Residual Disease
As noted above, disease burden at the time of transplant
has a strong impact on survival. This effect is also evident
when looking at more subtle levels of disease that
can be detected by sensitive methods of MRD detection
(especially RT-PCR assays for BCR-ABL). Thus, the detection
of MRD after induction and consolidation therapy
is fairly common in Ph+ ALL, and is associated with
an increase risk of relapse [103–105]. By using quantitative
RT-PCR for BCR-ABL, Pane et al. [104] found that
patients who achieved >3 log reduction after consolidation
had a significantly better DFS and OS. Moreover,
analysis of the MRD during the phase II Imatinib studies
showed that the kinetics in the reduction in the number
BCR-ABL predicted the group of “good responders”
with a longer time to progression [106]. Furthermore,
high levels of MRD at diagnosis, and an increase in
the level of MRD ³2 logs predicted patients at a high
risk of relapse [107].
MRD after HSCT also predicts relapse. Unlike the
chemotherapy setting, a significant percentage of patients
who undergo allogeneic HSCT become BCR-
@ 26%/22% 3y
ABL negative after transplant. The detection of MRD
by RT-PCR correlates strongly with subsequent relapse,
usually within 3 months; the risk seems to be higher for
patients with the p190 BCR-ABL transcript compared to
the p210 variant [10, 41, 98, 103, 105, 108, 109]. Moreover,
the MRD status prior to transplant has been shown to
be significantly predictive of EFS [41, 74, 110].
14.6 Conclusion
Despite advances in conventional chemotherapy and
targeted therapy, Ph+ ALL continues to be a very poor
prognostic variable in adult and pediatric ALL. A better
understanding of the molecular biology of BCR-ABL
may lead to advances in more active targeted therapies,
but for now, the only curative modality remains stem
cell transplantation. As advances in this modality increase,
the likelihood of potential cures with transplantation
combined with novel targeted therapy likely
looms at the best strategy for curative therapy.
References
Comments
Similar results for CR1 and >CR1
All patients studied in CR1
[95] Dunlop, et al. 1986–1995 19
EFS: 2/9 autologous, 2/11 MRD (12 CR1, 3 CR,
5 RLPS)
[42] Arico, et al. 1986–1996 38 *65% 5y
EFS with autologous transplant: 6/25
[100] Sierra, et al. 1988–1995 18 49% 2y
All matched unrelated donors
[96] Kroger, et al. 1990–1997 14 38% 3y
13 MRD, 6 URD, 5 autologous. DFS for
allogeneic transplants in 1 st CR 46% at 3y.
[97] Esperou, et al. 1992–2000 121 – 2 yr OS: 50% for CR1 and 17% for >CR1
[75] Thomas, et al. 1994–2002 140 **24% 5y
75 allogeneic, 65 autologous. 3 year DFS 15%
for autografted patients and 34% for allografted
MRD: matched related donor. URD: unrelated donor. (@): 26% 3y DFS for autologous bone marrow transplantation; 22% 3y DFS for allogeneic
bone marrow transplantation. (-) Not reported. (*) Estimated EFS in patients treated with HLA-Matched related donor. (**) Reported on 198
patients diagnose with Ph+ ALL and treated on protocol LALA-94.
1. Rubin CM, Carrino JJ, Dickler MN, Leibowitz D, Smith SD, Westbrook
CA (1988) Heterogeneity of genomic fusion of BCR and
ABL in Philadelphia chromosome-positive acute lymphoblastic
leukemia. Proc Natl Acad Sci 85(8):2795–2799