Contributions
Abstract: PB1751
Type: Publication Only
Background
Erythropoietin-refractory anemia is a serious problem and complicated causes should be ruled out in patients on dialysis. Acquired pure red cell aplasia (PRCA) may be hidden behind anemia of chronic kidney disease. Recently it was reported that PRCA patients with large granular lymphocyte frequently had STAT3 mutations (Oie ZY et al. J Hematol & Oncol 2013, Ishida F et al. Cancer sci 2014). Molecular or flow-cytometric analysis is useful for detecting a small amount of abnormal lymphocytes.
Aims
We conducted this study to determine the clinical characteristics and STAT3 mutations of patients with acquired PRCA on dialysis with lymphoproliferative diseases.
Methods
In our hospital, 4 patients were diagnosed as having acquired PRCA on dialysis with lymphoproliferative diseases after 2005. Patients were retrospectively studied for presenting feature, laboratory data, and clinical course. Surface markers of lymphocytes were examined by flow cytometric analysis, and T-cell receptor (TCR) rearrangements were examined by Southern blot analysis. Mononuclear cells were separated after obtaining written informed consent. STAT3 (Y640F and D661Y) mutations were examined by allele-specific PCR. Current study was conducted within the guidelines and with the approval of the institutional ethical committee.
Results
In spite of adequate administration of erythroid colony-stimulating factor, all 4 patients required blood transfusion due to erythropoietin-refractory anemia. Median leukocyte and lymphocyte counts at diagnosis were 4650/mL (range, 3180-4850) and 1794 mL (range, 1183-2859), respectively. Two patients (Cases 1 and 2) had low percentage of CD4+ CD8+ by flow-cytometry and TCR C beta1 and gamma rearrangements by Southern blot analysis. Another patient (Case 3) had high percentage of gamma-delta T cell component (66.2%) with TCR delta rearrangement. The other patient (Case 4) had high CD16+CD56+ NK cell percentage without TCR receptor rearrangement. The median duration from the start of dialysis to onset of PRCA was 13 years (range, 5-19 years). Of the 4 patients, only one patient (Case 3) had the mutations of the STAT3 gene (Y640F). This patient first received cyclophosphamide but he did not respond to the therapy. He subsequently received cyclosporine (CyA). The other three patients received CyA as an initial therapy, and it was effective in all 4 patients. Median follow-up were 7 years from diagnosis, and two patients died during follow-up period. One patient (Case 4) died of cardiac failure 7 years from the diagnosis. Another patient (Case 2) developed diffuse large B-cell lymphoma 5 years after the administration of CyA. He was treated with R-CHOP chemotherapy and complete remission (CR) was achieved. Although he had been in CR, he died of refractory pancytopenia with infection, 2 years after the lymphoma onset. The other two patients are still alive without blood transfusion for 6 and 7 years.
Conclusion
A proportion of erythropoietin-refractory anemia patients on dialysis have acquired PRCA associated with lymphoproliferative diseases. The combined analyses of flow-cytometry and TCR rearrangement of lymphocytes were useful for diagnosis of acquired PRCA associated with lymphoproliferative diseases. Further accumulations of patients were required for understanding the pathogenesis of lymphoproliferative diseases causing acquired PRCA on dialysis.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): STAT3, Pure red cell aplasia, Lymphoproliferative disorder
Abstract: PB1751
Type: Publication Only
Background
Erythropoietin-refractory anemia is a serious problem and complicated causes should be ruled out in patients on dialysis. Acquired pure red cell aplasia (PRCA) may be hidden behind anemia of chronic kidney disease. Recently it was reported that PRCA patients with large granular lymphocyte frequently had STAT3 mutations (Oie ZY et al. J Hematol & Oncol 2013, Ishida F et al. Cancer sci 2014). Molecular or flow-cytometric analysis is useful for detecting a small amount of abnormal lymphocytes.
Aims
We conducted this study to determine the clinical characteristics and STAT3 mutations of patients with acquired PRCA on dialysis with lymphoproliferative diseases.
Methods
In our hospital, 4 patients were diagnosed as having acquired PRCA on dialysis with lymphoproliferative diseases after 2005. Patients were retrospectively studied for presenting feature, laboratory data, and clinical course. Surface markers of lymphocytes were examined by flow cytometric analysis, and T-cell receptor (TCR) rearrangements were examined by Southern blot analysis. Mononuclear cells were separated after obtaining written informed consent. STAT3 (Y640F and D661Y) mutations were examined by allele-specific PCR. Current study was conducted within the guidelines and with the approval of the institutional ethical committee.
Results
In spite of adequate administration of erythroid colony-stimulating factor, all 4 patients required blood transfusion due to erythropoietin-refractory anemia. Median leukocyte and lymphocyte counts at diagnosis were 4650/mL (range, 3180-4850) and 1794 mL (range, 1183-2859), respectively. Two patients (Cases 1 and 2) had low percentage of CD4+ CD8+ by flow-cytometry and TCR C beta1 and gamma rearrangements by Southern blot analysis. Another patient (Case 3) had high percentage of gamma-delta T cell component (66.2%) with TCR delta rearrangement. The other patient (Case 4) had high CD16+CD56+ NK cell percentage without TCR receptor rearrangement. The median duration from the start of dialysis to onset of PRCA was 13 years (range, 5-19 years). Of the 4 patients, only one patient (Case 3) had the mutations of the STAT3 gene (Y640F). This patient first received cyclophosphamide but he did not respond to the therapy. He subsequently received cyclosporine (CyA). The other three patients received CyA as an initial therapy, and it was effective in all 4 patients. Median follow-up were 7 years from diagnosis, and two patients died during follow-up period. One patient (Case 4) died of cardiac failure 7 years from the diagnosis. Another patient (Case 2) developed diffuse large B-cell lymphoma 5 years after the administration of CyA. He was treated with R-CHOP chemotherapy and complete remission (CR) was achieved. Although he had been in CR, he died of refractory pancytopenia with infection, 2 years after the lymphoma onset. The other two patients are still alive without blood transfusion for 6 and 7 years.
Conclusion
A proportion of erythropoietin-refractory anemia patients on dialysis have acquired PRCA associated with lymphoproliferative diseases. The combined analyses of flow-cytometry and TCR rearrangement of lymphocytes were useful for diagnosis of acquired PRCA associated with lymphoproliferative diseases. Further accumulations of patients were required for understanding the pathogenesis of lymphoproliferative diseases causing acquired PRCA on dialysis.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): STAT3, Pure red cell aplasia, Lymphoproliferative disorder