The role of paroxysmal nocturnal hemoglobinuria clones in response to immunosuppressive therapy of patients with severe aplastic anemia

Abstract

Whether paroxysmal nocturnal hemoglobinuria (PNH) clone in aplastic anemia (AA) is a prognostic factor to immunosuppressive therapy is a subject of debate. We evaluated hematological responses to immunosuppressive therapy (IST) in severe AA (SAA) patients with or without the presence of a PNH clone. In 97 SAA patients who received first-line IST between January and December 2011, 24 (24.7 %) had a PNH clone prior to treatment, with a median clone size of 7.82 % (range 1.19-45.46 %). The response rates to IST for patients with or without a PNH clone were 66.7 and 50.7 % (P < 0.172), 79.2 and 57.5 % (P < 0.057), and 79.2 and 67.1 % (P < 0.264) at 3, 6, and 12 months, respectively. Combined rate of complete and good partial responses differed between patients with or without a PNH clone: insignificantly at 3 months (41.7 vs. 21.9 %, P < 0.058), but significantly at 6 (66.7 vs. 31.5 %, P < 0.002) and 12 (75.0 vs. 46.6 %, P < 0.015) months. Multivariate analysis revealed that a pretreatment neutrophil count of >0.2 × 10(9)/L is indicative of a better response, while the presence of a PNH clone is predictive to a higher combined rate of complete and good partial responses. This study demonstrated that the presence of a PNH clone could predict a better hematological response instead of a higher response rate in patients with SAA.

Diagnostic screening of paroxysmal nocturnal hemoglobinuria: Prospective multicentric evaluation of the current medical indications

“…In contrast, PNH testing for cases presenting with unexplained thrombosis in the absence of anemia or another cytopenia, as well as for patients diagnosed with other hematological/immunological disorders in the absence of a BM failure syndrome, emerged as worthless, with extremely low rates of PNH positivity. Overall, these results are in line with previous observations reported in the literature mostly in smaller patient series and specific diagnostic groups .…”

“…These results emphasize the need for PNH testing in AA patients of any age, including also younger AA cases . In line with our observations, previous studies have shown that GPI‐deficient cells are frequently found in AA and MDS patients, while they are detected only in few MPN cases . Despite the exact frequency of PNH+ AA cases varies substantially in the literature (range 22% to 89%) , it is currently estimated to be ≈40% of cases , as also found in our series with slight differences according to the age of the patients.…”

“…The efficiency of PNH testing among patients with BM failure syndrome has been more extensively investigated in the literature (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) due to the well-known association between the presence of GPI-deficient cells among AA patients and response to immunosuppressive therapy (23)(24)(25)(26)(27)(28)(29)(30)(31), as well as progression to symptomatic PNH (32). Overall, a BM failure syndrome associated with prior diagnosis of a hematological malignancy was the medical indication most frequently associated with PNH positivity in our series, both in adults and in children or adolescents.…”

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

“…However, the reliability of results obtained from minor PNH populations remains controversial. For example, several studies conducted on adults and/or children with AA reported that the presence of minor PNH populations was associated with a favorable response to IST [14,17,18,29,[31][32][33]. In contrast, a retrospective National Institutes of Health (NIH) study that included adults and children did not find differences between AA patients who did or did not respond to IST [10].…”

“…The utility of ARC in predicting IST outcomes has been confirmed in a proportion of reports, but not in others [12,[14][15][16][17]. Higher absolute neutrophil count (ANC) appears to be correlated with a better response rate of IST [15,18]; however, this result was not confirmed in Japanese and German children [12,19,20]. Further, the study of Japanese children demonstrated that lower white blood cell (WBC) count was indicative of a better response to IST rather than higher ANC [12].…”