The analysis also revealed a valuable consideration for the selection of donors, which could affect outcomes for older patients as well.

“…an unexpected finding,” Dr Onida said, “was that the patients undergoing allogeneic transplant from an unrelated donor seem to have a better outcome compared with the patients transplanted by a relative.”

His theories about the factors behind that result involve the age of the donor and the different ways transplants involving relatives and non-relatives are handled. Siblings would, usually, be of similar ages. So a patient over 45 “probably had a donor who was older than 45,” Dr Onida said. “And there are recent data showing that the age of the donor is really important for the outcome.”

Secondly, he posits that the use of anti-thymocyte globulin (ATG) to combat graft-versus-host disease could contribute to differences in immunological activity in the patients in his retrospective analysis.

“When we transplant patients with an unrelated donor we always perform some kind of T cell in vivo depletion using ATG,” he said. “And that’s been accepted all over the world. But when we did transplants from HMA identical siblings we didn’t use to add ATG.”

One of the challenges confronting researchers and, thus far, stymieing the development of effective therapies is the lack of understanding of the biological mechanisms driving aCML.

A study published in March aimed to clear up some of the mystery by identifying prognostically relevant mutations.4

“What we tried to do was, one, define the molecular makeup of the disease with this extensive sequencing project,” the study’s lead author, Dr Mrinal M. Patnaik, of the Division of Hematology at the Mayo Clinic in Rochester, Minnesota, explained, “and then, based on what we found and what we are currently doing, we want to see if we can find some targeted therapies that might be effective either in improving outcomes in the disease or…to try to help cure the disease.”

RELATED: Improvement Needed in CML BCR-ABL1 Monitoring

The study analyzed a variety of clinical and laboratory variables, as well as relevant gene mutations, in 25 patients. It was found that increasing age, low hemoglobin, and TET2 mutations were independently prognostic.

“At least we understand the epigenetic pathways that are deregulated in the disease,” Dr Patnaik said. “There is nothing major in terms of an immediate therapeutic target, but at least it is defining the biology so that people working in this field can continue to define targets downstream to these mutations to see if they can be targeted.”

References

  1. Cancer stat facts: chronic myeloid leukemia (CML). National Cancer Institute website. https://seer.cancer.gov/statfacts/html/cmyl.html. Accessed April 2017.
  2. Dao KT, Tyner JW. What’s different about atypical CML and chronic neutrophilic leukemia? Hematology Am Soc Hematol Educ Program. 2015;2015:264-71. doi: 10.1182/asheducation-2015.1.264
  3. Onida F, de Wreede LC, van Biezen A, et al. Allogeneic stem cell transplantation in patients with atypical chronic myeloid leukaemia: a retrospective study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol. 2017 Mar 28. doi:10.1111/bjh.14619 [Epub ahead of print]
  4. Patnaik MM, Barraco D, Lasho TL, et al. Targeted next generation sequencing and identification of risk factors in World Health Organization defined atypical chronic myeloid leukemia. Am J Hematol. 2017 Mar 17. doi: 10.1002/ajh.24722 [Epub ahead of print]