INTRODUCTION: Published cases of hematological malignancies following double lung transplantation in adults are few, as are cases reported in cystic fibrosis patients. Most cases described are after renal transplantation. Acute myeloid leukemia has been described in the pediatric cystic fibrosis population. Here, we present an adult CF lung transplant patient with AML-M5.
CASE PRESENTATION: A 30 year old Caucasian female with CF genotype ΔF508/W1282X diagnosed at age three years, presented with dyspnea on exertion, intense bilateral hip pain, new onset leukocytosis and peri-orbital ecchymosis. Double lung transplant had been performed eleven months previously. IVIG infusions were initiated after six weeks for post transplant specific anti-HLA antibodies. Pre transplant respiratory infections included MRSA and multi-drug resistant Pseudomonas. MRSA bronchitis was treated successfully one month after transplantation. She was compliant with immunosuppressive medications azithioprine, tacrolimus and prednisone, and all post transplant infection prophylaxis. Medical history included a seizure disorder treated with valproic acid, cystic fibrosis related diabetes mellitus and osteoporosis. At a routine clinic visit prior to ICU admission, white blood cell count was 3.9x103/μL, with 44% lymphocytes and no blast cells. Hemoglobin was 12.7. FEV1 was 61% at baseline. MRI of hip joints done for fatigue and hip pain, showed an area of abnormal marrow signal in the left iliac bone. Total body bone scan subsequently performed did not reveal uptake abnormalities or avascular necrosis. Her symptoms worsened and follow up CBC three weeks later showed WBC 255x103/μL, 7% lymphocytes and 90% blasts. She was admitted to the Intensive Care unit for observation and was alert, afebrile and hemodynamically stable. Oxygen saturation was 98% on room air. Pertinent findings on exam were pallor, mild dyspnea, bilateral hip pain, peri-orbital ecchymosis and decreased breath sounds. However, she rapidly decompensated, and despite resuscitative meausues, developed multi-organ failure and disseminated intravascular coagulopathy ultimately leading to her death. Flow cytometry confirmed acute monoblastic leukemia (FAB M5a) post mortem. Blood cultures also revealed methicillin resistant staphylococcal infection. Bone marrow biopsy was not performed.
DISCUSSION: While post lung transplant lymphoproliferative disorders are a recognized entity, acute leukemia presentation is rare. Certain gastrointestinal malignancies in CF patients have been described and this risk is further increased post organ transplantation, possibly secondary to immunosuppressive therapies. Chronic inflammation and failure to thrive are thought to predispose to pancreatic and digestive tract cancers. Mutations or partial deletions of chromosome 7 have been demonstrated in AML and myelodysplastic syndrome. The CFTR mutation lies on 7q31. Increased risk for AML has not been demonstrated in CF patients with ΔF508 mutation, but carriers of the mutation may be predisposed to developing AML.
CONCLUSIONS: Research on hematological malignancies in CF patients after lung transplant with co-existing ΔF508 mutations is required. Bone marrow biopsy may be indicated earlier in post transplant patients with ΔF508 mutation. Recurrent infections in CF patients causing chronic inflammation may cause cellular damage predisposing to malignancy, particularly in the context of immunosuppressive agents. Further reports are needed to clarify the prevalence and significance of AML in CF patients after lung transplantation.
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Reference #3 Maisonneuve, P, FitzSimmons SC, Neglia JP, et al. Cancer Risk in Non transplanted and Transplanted Cystic Fibrosis Patients: A 10-Year Study. J Natl Cancer Institute. 2003; 95: 381-387
DISCLOSURE: The following authors have nothing to disclose: Zahra Mathura, Rodney Folz, David Hiestand
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