PS1121 ABSENCE OF GPI‐NEGATIVE CELLS AT DIAGNOSIS AND LOW NEUTROPHIL COUNT 2 MONTHS AFTER ATGAM BASED TREATMENT ARE ASSOCIATED WITH LOWER 6‐MONTH RESPONSE RATE IN ADULTS WITH (VERY) SEVERE APLASTIC ANEMIA
Authors: J. Tjon, L. Bogers, L. de Wreede, M. de Groot, S. Langemeijer, H. Koene, E. Meijer, E. Nur, M. Raaijmakers, R. Raymakers, T. Snijders, S. Halkes
Journal: HemaSphere (2019)

Background: In aplastic anemia (AA), allogeneic stem cell transplantation (AlloSCT) is proposed as first line treatment for young patients with a sibling donor. For all other patients, ATGAM‐based immunosuppressive therapy (IST) is the treatment of choice. After IST, recovery of blood counts can take up to 6 months. Patients with (very) severe AA ((V)SAA), with a neutrophil count &lt;0.2 or &lt;0.5 x 10 9 /L respectively, remain at risk for infectious complications until blood count recovery. Timely identification of patients less likely to respond to IST could lead to earlier selection for second line treatment (either alloSCT or second line IST) in order to prevent prolonged neutropenia. In AA, the presence of glycophosphatidylinositol (GPI) negative cell clones at diagnosis is associated with a better response to IST in some studies. We hypothesized that the absence of GPI negative cells (&lt;0.1%) before IST and low neutrophil count 2 months after start of treatment are associated with a lower response rate 6 months after IST in (V)SAA patients. Aims: To Determine whether the presence of GPI negative cell clones before IST and a neutrophil count &lt;0.2 x 10 9 /L 2 months after IST can predict for treatment refractoriness at 6 months in adult (V)SAA patients. Methods: The Dutch registry of adults with acquired aplastic anemia receiving ATGAM (40 mg/kg for 4 days intravenously) and ciclosporin as first‐line treatment contains data on all consecutive patients treated in 8 major hospitals (LUMC, A‐UMC, UMCG, R‐UMC, UMCN, EMC, MST and AZN) including baseline and monthly follow‐up data. Response at 6 months was defined as transfusion independency and neutrophil count &gt;0.5 x 10 9 /L. Overall survival (OS) was evaluated with the Kaplan‐Meier method. Results: Between 2012 and February 2019, 73 patients, 47 with SAA and 26 with VSAA were registered. Median age at start of IST was 58 years (18–79) and the median follow up time was 21 months. The 6‐month OS probability was 96% for SAA and VSAA combined (88% for VSAA and 100% for SAA). 62 patients were evaluable for response 6 months after start of IST. Response was seen in 35 patients (56% (CI 44–68%)). At diagnosis, 36 patients had a detectable GPI negative cell clone. In 25 patients, GPI‐negative cells were not detected and in 12 patients the presence of GPI‐negative cells was not tested. The response rate 6 months after start of IST for patients with a GPI‐negative clone at diagnosis was 63% (CI 47–80%) versus 40% (CI 20–60%) for patients without a GPI‐negative clone. Median neutrophil count 2 months after start of IST was available for 57 patients. The majority of the patients (53) had a neutrophil count ≥ 0.2 x 10 9 /L and in this group the response rate at 6 months was 58% (CI 45–71%). In contrast, of the 4 patients with neutrophil counts &lt;0.2 x 10 9 /L at 2 months after IST, 1 died 3 months after IST and the remaining 3 patients were alive but non‐responding to IST at 6 months. Summary/Conclusion: Our analysis of a relatively old (V)SAA patient cohort treated with ATGAM based IST suggests that presence of GPI negative cells at diagnosis and the neutrophil count at 2 months could be used to predict response to first line IST. This knowledge could aid in the decision to start second line treatment (alloSCT or second‐line IST) in this vulnerable patient group.