Contributed by Eumenia Castro, MD, PhD and Lydia Contis, MDFINAL DIAGNOSIS
CHRONIC MYELOGENOUS LEUKEMIA, BCR-ABL1 POSITIVE, CHRONIC PHASE
DISCUSSION
Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that originates in a abnormal pluripotent bone marrow stem cell. The median age at diagnosis is in the 5th and 6th decades of life (WHO, 2008). CML occurring in children is a rare diagnosis, accounting for less than 10% of all CML and less than 2% of all pediatric leukemias (Hara et al, 2010, Singhal et al, 2010, Aperley, 2009, Radhakrishnan et al, 2009, Suttorp et al, 2009, Wechalekar & Parande, 2007, Chinnappan et al, 2000, Plezbert, 1994, Ghione et al, 1986). Adult patients who undergo solid organ transplantation are at increased risk of developing malignancies such as lymphoid tumors, post transplant lymphoproliferative disorders and skin tumors (Buell et al, 2005). In pediatric solid organ transplant recipients, this trend changes as post-transplant lymphoproliferative disorders (PTLD) are most common (Nalesnik, 2001, Penn, 1998; Shapiro et al, 1999). CML developing post solid organ transplantation has rarely been reported in adult patients (Fontana et al, 2008, Tremblay et al, 2002, Mignozzi et al, 2001, Sanz et al, 1996) and only two cases have been reported in children (Silliman et al, 2003, Mignozzi et al, 2001). The case of CML developing in a 10 year old female, 8 years after liver transplantation represents the youngest patient in the literature to develop CML post transplant. All previously reported cases of CML post transplant affected older adolescents and adult patients, the population in which CML is more frequently seen (Silliman et al, 2003, Tremblay et al, 2002, Mignozzi et al, 2001, Sanz et al, 1996). However, in the adult transplant population, it remains a rare event. CML is a myeloproliferative neoplasm that occurs most commonly in the 5th and 6th decades of life (WHO, 2008). Feww cases occur per year in the pediatric population ), while the incidence is higher in adolescents (age 15-19 years) at 1.2 per million per year than in younger children (0-14 years) where it occurs in an incidence of 0.6-0.8 per million per year (Hara et al, 2010, Singhal et al, 2010, Aperley, 2009, Radhakrishnan et al, 2009, Suttorp et al, 2009, Wechalekar & Parande, 2007, Chinnappan et al, 2000, Plezbert, 1994, Ghione et al, 1986). Thus, The development of CML in young patients, in a post solid organ transplant setting EBV related PTLDs occur far more commonly in this population than CML. Therefore, this case highlights the importance of recognizing the pathological features associated with this rare disease in the setting of post transplant hematologic neoplasia in children. Of note, this patient's post transplant course was also complicated by the development of a hepatic Epstein-Barr virus-associated smooth muscle tumor in addition to a CD20 positive infectious mononucleosis-like post transplant lymphoproliferative disorder which were treated with anti-viral therapy as well as rituximab six years before developing CML. Whether the immunosuppressive therapy associated with the use of Rituximab and anti-viral therapy may have contributed to the development of CML in our patient remains difficult to establish. In kidney transplant recipients who developed CML post transplant, immunosuppressive therapy appeared to be a contributory factor (Silliman et al, 2003, Tremblay et al, 2002, Mignozzi et al, 2001, Sanz et al, 1996). All the reported patients (how many?) who developed CML after kidney transplant received immunosuppression with azathioprine, and therefore the type of immunosuppressive therapy was considered the most important risk factor for the development CML (Silliman et al, 2003, Tremblay et al, 2002, Mignozzi et al, 2001, Sanz et al, 1996). In liver transplant patients, there are only two cases reported in the literature where the patients developed CML (Silliman et al, 2003, Fontana et al, 2008). The first report in a pediatric population occurred in a 16 year old boy who developed Philadelphia chromosome-positive T- lymphoblastic leukemia after liver transplantation, in whom Cyclosporine A was used as the immunosuppressive therapy (Silliman et al, 2003). The latter report also included 3 adult patients, 2 status post liver transplant and one post kidney transplant, who developed atypical CML with use of tacrolimus as immunosuppressive therapy (Fontana et al, 2008). These reports favor the role of immunosuppressive therapy as contributory to the development of CML in solid organ transplant recipient patients. The patient in this case was not however receiving immunosuppression therapy when she developed CML 8 years after, it was suspended. The role of anti-viral as well as rituximab therapy in the development of CML in our patient remains a consideration. This case also highlights the benefit of cytogenetic and molecular studies in distinguishing a reactive process from a clonal hematopoietic neoplasm in a transplant recipient. with abnormal blood counts. In summary, this case represents that of CML developing in a 10 year old female, 8 years post liver transplant. To our knowledge, this is the first reported case of CML developing in a young child post liver transplant. As CML is uncommon in a pediatric population, the role of immunosuppression in the development of this hematopoietic neoplasm should be considered.
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Contributed by Eumenia Castro, MD, PhD and Lydia Contis, MD
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