tacrolimus and Precursor-T-Cell-Lymphoblastic-Leukemia-Lymphoma

Topics: Abnormal Karyotype; Adult; Antigens, CD; Biomarkers, Tumor; Burkitt Lymphoma; Diagnosis, Differential; Humans; Immunosuppressive Agents; Lung Transplantation; Lymph Nodes; Male; Postoperative Complications; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-Lymphocyte Subsets; Tacrolimus

Tacrolimus is an immunosuppressive drug that is used to lower the activity of the patient's immune system to prevent organ rejection. Unfortunately, there is limited data regarding the therapeutic equivalency of generic tacrolimus formulations especially in children. We report the case of a pediatric patient having an inability to achieve a therapeutic trough level for tacrolimus after conversion from brand name to the generic formulation.. A 17-month-old male patient diagnosed with T-cell acute lymphoblastic leukemia underwent allogeneic stem cell transplantation. The patient initially received intravenous (i.v.) tacrolimus for graft-versus-host disease (GVHD) prophylaxis and achieved therapeutic levels. The patient was then switched to an oral brand formulation of tacrolimus, and was able to maintain trough levels within the therapeutic range. After being discharged, the patient received the generic formulation of tacrolimus from an outside pharmacy and the care team was unable to reach therapeutic levels despite multiple dose escalations. Returning to brand name tacrolimus resulted in prompt achievement of therapeutic levels.. A likely etiology for the inability to achieve therapeutic trough levels in this patient is the change in formulation from brand formulation to generic version. Other factors including drug-drug interaction, preparation of the medication by a different pharmacy, drug-food interaction and genetic factors were also considered. Physicians and pharmacists must be aware of the inability to achieve targeted therapeutic concentrations of tacrolimus resulting from the conversion of brand name to the generic formulation until these generic formulations are tested in clinical trials in a pediatric population.

Topics: Drug Substitution; Drugs, Generic; Graft vs Host Disease; Humans; Immunosuppressive Agents; Infant; Male; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Stem Cell Transplantation; Tacrolimus; Therapeutic Equivalency; Transplantation, Homologous

Post-transplant lymphoproliferative disorders of T-cell origin are quite uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three liver transplants, initially for biliary atresia and subsequently for graft failure due to chronic rejection. He had received immunosuppression with cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL occurred 16 years after the first liver transplant. This case highlights the challenge for classifying rare neoplasms occurring in recipients of solid organ transplants that are currently not recognized to lie within the spectrum of post-transplant lymphoproliferative disorders. Given the long interval between the liver transplants and the development of T-ALL, a coincidental occurrence of the leukaemia cannot be ruled out. However, the potential roles of immunosuppressive therapy and other co-morbid conditions of the individual as possible risk factors for the pathogenesis of T-ALL are discussed.

Topics: Adolescent; Biliary Atresia; Causality; Clone Cells; Comorbidity; Cyclosporine; Diagnosis, Differential; Disease Susceptibility; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Leukemia, Radiation-Induced; Liver Transplantation; Lymphoproliferative Disorders; Male; Muromonab-CD3; Postoperative Complications; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Radiography; Remission Induction; Reoperation; Tacrolimus; Time Factors