Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome in a Child With Klinefelter Syndrome
Klinefelter syndrome is characterized by gynecomastia, hypogonadism, small testes, elevated levels of follicle-stimulating hormone and an extra X chromosome (ie, 47,XXY).1 These patients tend to have an increased risk of developing male breast cancer and mediastinal germ cell tumors.2,3 Hematologic malignancies including acute or chronic leukemia are also observed in these patients,4 but only a few case reports with Klinefelter syndrome who developed myelodysplastic syndrome (MDS) were published.4–7
An 11.5-year-old boy was referred with complaints of fever, headache and cough, complicated with pancytopenia. He had a 3-week history of upper respiratory symptoms. Developmental milestones were normal; however, he had low grades at school. On admission, the physical examination revealed microcephaly, petechiae, ecchymosis, rales, minimal subcostal retraction, and hepatosplenomegaly. His height was 158 cm (at 75 to 90 percentile), his weight was 40 kg (at 25 to 50 percentile). Penile length was normal. He had scrotal hyperpigmentation. Testes were bilaterally descended; testicular volume was 6/6 mL. Systemic examination revealed no other abnormalities.
Hematologic tests demonstrated pancytopenia with a hemoglobin of 9.7 g/dL, platelet count 4000/µL, white blood cell count 2600/µL. Peripheral blood smear demonstrated; 16% blasts, 2% neutrophils, 74% lymphocytes, 8% monocytes with 3 lineage dysplasia. Bone marrow aspiration smear showed; 12% blasts, 1% promyelocytes, 3% metamyelocytes, 35% lymohocytes, 33% normoblasts, 13% myelocytes, 2% neutrophil, and 1% monocytes (Fig. 1). He was diagnosed with MDS. Phenotypical characteristics and chromosome analysis—both from bone marrow and peripheral blood—which demonstrated 47,XXY karyotype led to the diagnosis of Klinefelter syndrome. Chest computerized tomography was consistent with pulmonary infection and the patient was given broad spectrum antibiotics (vancomycin, meropenem, amikacin, clarithromycin, and trimethoprim sulfamethoxazole). After treatment of pulmonary infection, the patient underwent hematopoietic stem cell transplantation (HSCT) from his HLA-matched sibling. The transplant characteristics and the results of transplantation were shown on Table 1. Ten months after HSCT, he was admitted for shortness of breath. On examination he had rales and ronchi. His respiratory function tests revealed obstructive pattern. High resolution computerized tomography of the chest showed focal opacities with ground—glass densities in superior segment of inferior lobe of the right lung. He was diagnosed with bronchiolitis obliterans. He benefited from formoterol fumarate clinically and his respiratory function tests improved. There was not any evidence of chronic graft versus host disease other than bronchiolitis obliterans. At 8 years of follow-up, the patient is still in remission for MDS with normal hematological parameters and normal pulmonary function. His developmental status is within normal limits. He is being followed up with hypergonadotropic hypogonadism.
In children and adolescents, MDS occurs in both de novo and secondary forms. Secondary MDS is seen in patients who received chemo or radiation therapy (therapy-related MDS), in patients with inherited bone marrow failure disorders, following acquired aplastic anemia, and as familial MDS.8 Association of Klinefelter syndrome and MDS has been reported in only a few patients and all of these patients were adults and none of them underwent HSCT.4–7 Interestingly, in our case MDS developed in childhood and he was successfully treated with HSCT.