BCR‐ABL positive cells and chronic myeloid leukemia in immune suppressed organ transplant recipients

Abstract

The constitutively activated tyrosine kinase activity of the p210(bcr-abl) fusion protein, generated by a t(9;22)(q34;q11) chromosomal translocation, is pathogenetically associated with chronic myeloid leukemia (CML). However, mechanisms contributing to the expansion of a BCR-ABL positive clone are largely obscure. In the presence of an impaired immune surveillance, cells carrying any of these alterations may become phenotypically relevant. Therefore, immunosuppressed solid organ recipients represent an optimal population to investigate the frequency of mRNA products of this translocation. Blood leukocytes were studied in 201 individuals (100 organ recipients and 101 control individuals) for the presence of BCR-ABL transcripts by a nested-reverse transcriptase-polymerase chain reaction assay, routinely used in our institution. In 5/100 immunosuppressed patients, at least one out of two RT-PCR products was bcr-abl positive while all controls were negative. These findings were extended by four CML cases of organ transplant recipients (three renal and one liver transplants). Three of these cases developed CML in a total of 2088 transplantations in 9 yr, suggesting a higher incidence of CML in these patients.

Elevated incidence of chronic myeloid leukaemia in immunosuppressed solid organ transplant recipients

“…Importantly, in this series of patients we did not observe any difference in response to treatment with imatinib as compared to immunocompetent patients suggesting these patients can be managed according to standard treatment algorithms. Single cases of CML in SOT recipients have been previously reported (le Coutre et al , ), but this is the first estimate of incidence. It remains to be determined to what extent factors, such as type of immunosuppression, HLA‐type and latency between transplantation and diagnosis of CML, may contribute to this phenomenon.…”

Clinical Lessons to Be Learned from Patients Developing Chronic Myeloid Leukemia While on Immunosuppressive Therapy after Solid Organ Transplantation: Yet Another Case after Orthotopic Heart Transplantation

“…Thus, CML developing in patients following SOT may be triggered by the effects of concomitant application of immunosuppressive drugs. In line with this hypothesis we previously compared by rt-PCR the BCR-ABL1 status in patients following SOT but without CML and indeed detected 5% low-level PCR positivity in these patients as compared to none in a control group without immunosuppression [ 21 ]. Finally, in a recently published article the risk to develop CML in patients after SOT was calculated to be more than 20-fold higher as in the normal population [ 26 ].…”

“…In this paper we describe another patient with chronic phase CML following orthotopic heart transplantation and immunosuppression. As in our previous article we discussed the various biological mechanisms that may contribute to CML following immunosuppression; we here provide an overview on all published cases and focus on individual aspects of the clinical management in this specific cohort [ 21 ].…”

Pediatric secondary chronic myeloid leukemia following cardiac transplantation for anthracycline‐induced cardiomyopathy

“…Three retrospective studies and several individual case reports reviewed cases of secondary CML in a variety of diseases including untreated malignancies, immunosuppression therapies and solid organ transplants without underlying malignancy [3,4,[10][11][12][13]. None of the studies could render an association between chemotherapy and secondary CML.…”