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Predicting and facilitating survival of pediatric cancer patients: The ALC story

2010; Wiley; Volume: 55; Issue: 6 Linguagem: Inglês

10.1002/pbc.22715

1545-5017

Pete Anderson,

Hematopoietic Stem Cell Transplantation

EXTRA, EXTRA read all about it! We can get a snapshot of our patient's future with a very inexpensive blood test. Fortunately, this test is already done by nearly every pediatric oncologist when they monitor blood counts for chemotherapy toxicity. Although pediatric oncologists commonly use the Absolute Neutrophil Count (percentage of PMN × wbc = ANC) to determine infection risk and when leucocyte recovery seems adequate to begin the next chemotherapy cycle, the Absolute Lymphocyte Count recovery (percentage lymphocytes × wbc = ALC) may be more important in the long run. Again, better ALC recovery is associated with significantly superior survival. The MD Anderson Orlando group reports in this issue of Pediatric Blood & Cancer significantly improved survival in patients with osteosarcoma who recover lymphocytes more rapidly on day 14 after initial chemotherapy. About 2/3 of their patients had recovery of ALC to >800 cells/µl on day 14 after initial chemotherapy cycles. These children achieved excellent survival (5-year overall survival 92%) compared to those that did not recover lymphocytes quickly (5-year overall survival 33%; P = 0.0013). Is this just luck of having resilient lymphocytes and better survival, or should we start thinking about how to facilitate ALC recovery and possibly improve a cancer patient's survival? Porrata and coworkers at Mayo Clinic have shown ALC recovery is a powerful predictor of survival in many different hematologic malignancies 1, 2 and breast cancer 3. ALC recovery is associated with significantly better survival in children and young adults with Ewing sarcoma in two different data sets 4, 5. ALC recovery was significant and independent of minimal residual disease (MRD) status in predicting leukemia survival and may possibly help redefine MRD-based risk stratification in pediatric ALL 6. In this study from three centers, ALC improvement was shown to be a continuous variable (i.e., each 100 lymphocytes/µl increase improved survival 4%) and ALC >1,500 cells/µl at end of induction predicted an excellent outcome in this cohort (80% EFS, 92% OS; P = 0.001). Thus, the osteosarcoma ALC results reported in this issue of Pediatric Blood and Cancer are probably part of a general phenomenon, that is, a more rapid ALC recovery after chemotherapy is associated with superior survival. Conversely, persistent and prolonged lymphopenia after chemotherapy has been associated with poor outcomes in a wide variety of cancers 7. Why? Better ALC recovery may be associated with better nutrition including glutamine supplementation 8. However, lymphocytes may have direct anti-tumor effects as well. Given the simplicity of monitoring ALC recovery, the ALC recovery information might help guide us concerning who needs more versus less therapy for osteosarcoma and other pediatric malignancies in the future. These data we need to prospectively collect and analyze. What are the means to facilitate ALC recovery? A single dose of dexamethasone decreases lymphocytes; exercise improves lymphocyte numbers 9. Since dexamethasone is very commonly used as an anti-emetic during chemotherapy of osteosarcoma and many other pediatric cancers, perhaps we should use dexamethasone as an anti-emetic with more caution until effects of those treated with dexamethasone versus no dexamethasone are studied. Certainly nowadays there are many effective means to reduce nausea. For example in my practice, long-acting 5HT anti-emetics (e.g., palonosetron daily × 4 days, granisetron BID or as a transdermal patch) combined with aprepitant are so effective that I do not use dexamethasone as an anti-emetic even with the very highly emetogenic doxorubicin plus cisplatin osteosarcoma chemotherapy. How a chemotherapy regimen is given may also make a difference. For example we give osteosarcoma chemotherapy without hospitalization. Outpatient chemotherapy may facilitate better nutrition and enteral intake at home instead of the hospital. Finally, lymphocytes use glutamine for fuel. There is abundant evidence that glutamine supplementation helps and does not hurt cancer patients 10. Attention to avoiding inadvertent starvation by multiple NPO episodes, such as NPO for scans and procedures (e.g., biopsy and/or line placement), avoiding poor oral intake after chemotherapy, and facilitating a diet high in protein with glutamine supplements may be a relatively easy way to help boost ALC recovery. Future means to speed ALC recovery may also involve choices of treatment regimens that affect lymphocytes less. Such studies may show the way for more effective chemotherapy regimens that are not only less toxic to ALC recovery but improve survival after a cancer diagnosis.