Pediatric ALL patients may have slightly higher risk for second cancer

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Survivors of standard-risk acute lymphoblastic leukemia (ALL) may have a slightly increased risk for second cancers and several chronic medical disorders compared with their siblings, new research suggests.

"This study illustrates that in addition to an excellent probability of survival, children with newly diagnosed standard-risk ALL have a good probability of long-term health and socio-economic outcomes (marriage, education, independent living, income) similar to their siblings," wrote senior author Dr. Paul C. Nathan of The Hospital for Sick Children in Toronto, Ontario, Canada, in an email to Reuters Health.

"Unfortunately, a minority of survivors will suffer adverse health or psychosocial outcomes. For most, though, the short- and long-term prognosis after the devastation of a leukemia diagnosis is good," he wrote.

"Survivors of standard risk ALL will certainly need lifelong medical care adapted to the specific risks arising from their prior therapy. However, given the low risk for serious morbidity, this care can be provided by a primary care physician who has access to the survivor's treatment history, care plan, and a mechanism for referral back to the cancer center if serious morbidity arises," he said.

Using data from the North American Childhood Cancer Survivor Study (CCSS) on five-year survivors of childhood cancer diagnosed between 1970 and 1986, Dr. Nathan and colleagues looked at the risk of late effects in children with standard-risk ALL treated with protocols of the day to estimate the risks of late effects in similar patients diagnosed today.

The authors looked at self-reported health, health status, and socioeconomic outcomes in 556 (13%) of 4,329 members of the CCSS aged 1.0 to 9.9 years when diagnosed.

As reported online June 20 in The Lancet Oncology, six (1%) survivors developed a later malignant neoplasm (standardized incidence ratio 2.6).

According to the authors, 107 children in each group (survivors and siblings) needed one-year follow up to observe one extra chronic health disorder in the survivor group.

Also, the authors say, 415 participants in each group would need to be followed for one year to observe one extra severe, life-threatening, or fatal disorder in the survivor group.

At a median follow up of 18.4 years (range 0.0-33.0), 28 (5%) of participants had died (standardized mortality ratio 3.5), 16 (57%) from causes other than ALL recurrence.

Survivors did not differ from siblings in their education level, rate of marriage, or independent living. But compared with siblings, standard-risk ALL survivors had a slightly increased risk for second cancers and several chronic medical disorders.

Dr. Smita Bhatia of City of Hope in Duarte, California, who was not involved in the study, advises caution when applying the findings from this study to today's patients.

"While the authors attempted to simulate contemporary therapeutic regimen situations, regimens have continued to evolve and it was not clear whether the doses of anthracyclines/cyclophosphamide used in the CCSS mirrored that used in contemporary protocols. Further, very few patients were exposed to these agents or dexamethasone, and again the schedule is not available," she wrote in an email.

"To extrapolate findings from patients treated in the 1970s to those treated now would require that we ensure that we are capturing the doses and schedules of the therapeutic regimens. Given that salvage strategies have changed so dramatically, mortality rates would be different in more contemporary eras," she cautioned.

"The strengths of the study include the long follow up of the survivors and a comparison group that included siblings. These patients are at increased risk for certain chronic health conditions such as osteonecrosis and cataracts, but because this study relies on self-report of complications, subtle complications may be under-reported, including osteoporosis (unless the patients are tested for it or develop fractures), cognitive dysfunction, and cardiac dysfunction that have not resulted in overt heart failure," she wrote.

In an editorial, Dr. Jeanette Falck Winther of the Danish Cancer Society Research Center in Copenhagen and Dr. Kjeld Schmiegelow of the University of Copenhagen say that with almost all patients surviving today, long-term quality of life and health challenges need to be addressed.

"Novel strategies are needed that ensure the capture of all relevant late effects; identify host factors that put some patients at the highest risk of such side-effects due to, for example, host genome variants, co-medication, or behavior; and identify patients who can be cured by less intensive treatment to avoid these late effects. New milestones on the road towards cure are still needed," they write.

Dr. Nathan added, "Pediatric oncologists have been striving to achieve excellent survival with minimal long-term toxicity in children with ALL and these results illustrate the success of this effort to focus not just on the cure, but on the quality of that cure."

SOURCE: http://bit.ly/1lzMeLV

Lancet Oncol 2014.

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