A case report of secondary autograft failure due to Gaucher disease
To the Editor: Recently, Mistry et al. [1] suggested that diagnostic delays in Gaucher disease (GD) resulted in severe disease manifestations. We present a case where the delayed treatment of known GD after transplant led to secondary engraftment failure. A 69-year-old Ashkenazi male with a history of asymptomatic GD underwent autologous stem cell transplant (ASCT) for relapsed non-Hodgkin's lymphoma (NHL) lymphoma. His GD was diagnosed with his initial presentation of lymphoma with Gaucher cells in bone marrow. His initial lymphoma was treated with rituximab, cyclophosphamide, doxorubicin, prednisolone (R-CHOP) and achieved complete remission for 3 years. Reoccurence was detected on routine positron emission tomography (PET) and he was referred for ASCT. Prior to transplant, his CBC showed a white blood cell (WBC) count of 8.9 Â 10 9 /L, hemoglobin of 14.1 g/dL, and platelets of 142 Â 10 9 /L. No positron emission tomography and computerized tomography (PETCT) was available.
He received rituximab, ifosfamide, carboplatin, etoposide (R-ICE) followed by carmustine, etoposide, cytarabine, melphalan (BEAM) and ASCT. Neutrophil engraftment occurred on day þ12 but was followed by an absolute neutroprhil count (ANC) nadir of 0.85 Â 10 9 /L on day þ93 requiring filgrastim. Platelet engraftment occurred on day þ35, but platelets were never >45 Â 10 9 /L. His average hemoglobin was 9.1 g/dL despite blood transfusions and weekly epoetin alpha administration. At þ90 days, a bone marrow biopsy (see Fig. ) showed infiltrates of Gaucher cells but no evidence of lymphoma, and GD evaluation was initiated.
GD was confirmed by enzyme studies. Mutational analysis showed homozygosity for the N370S (1226G) mutation. Evaluation revealed diffuse infiltration of the femurs with increased marrow activity, mild splenomegaly (seen on PETCT with cranial-caudate measurement of 13.2 cm, normal <12 cm), osteopenia (seen on dual-energy x-ray absorptiometry (DEXA) scan with a hip bone density of À1.18), and an elevated chitotriosidase level (448 mol/mL, normal <300). The patient refused to have an MRI; therefore, liver and spleen volumes are unavailable. Enzyme replacement therapy (ERT) with imiglucerase at 60 U/kg IV every 2 weeks was started on day þ153. Peripheral counts have improved after ERT during these past 8 months. Prior to ERT, his platelets were >45 Â 10 9 /L, but after ERT, they have increased to >70 Â 10 9 /L. He has not required blood transfusions, and epoetin alpha was last needed 42 days after ERT. At 1 year posttransplant, his CBC showed an ANC of 2.07 Â 10 9 /L, hemoglobin of 11.4 g/dL, and platelets of 73 Â 10 9 /L, and a PETCT found NHL remission with a normal spleen (cranial-caudate measurement of 11.4 cm) with DEXA pending.
Prior to transplant, he was asymptomatic with mild thrombocytopenia. After transplant he was pancytopenic requiring transfusion and growth factor support until the initiation of ERT. Gaucher cells were resistant to chemotherapy and may have contributed to secondary graft failure. It is interesting to speculate whether the chemotherapy, transplant, or growth factor support may have accelerated the GD phenotype by causing accelerated bone marrow turnover and increased substrate loading. In summary, patients with GD should be carefully evaluated in anticipation of high-dose chemotherapy and ASCT. ERT may be indicated in anticipation after ASCT to avoid secondary graft failure.