Predicting response to immunosuppressive therapy in childhood aplastic anemia

Abstract

9/L or more (P=0.0003), followed by shorter interval between diagnosis and therapy (P=0.01), and male sex (P=0.03). In conclusion, pre-treatment clinical and laboratory findings influence response to therapy. The finding that response rate worsens with increasing interval between diagnosis and treatment highlights the importance of prompt immunosuppressive therapy for patients with aplastic anemia.Key words: aplastic anemia, children, immunosuppressive therapy, predictive marker.Citation: Yoshida N, Yagasaki H, Hama A, Takahashi Y, Kosaka Y, Kobayashi R, Yabe H, Kaneko T, Tsuchida M, Ohara A, Nakahata T, Kojima S. Predicting response to immunosuppressive therapy in childhood aplastic anemia. Haematologica 2011;96(05):771-774. doi:10.3324/haematol.2010 This is an open-access paper. ABSTRACT ISTAll patients were treated with a combination of intravenous ATG (Lymphoglobulin; Genzyme, Cambridge, USA) at 15 mg/kg/day for five days and oral CyA at 6 mg/kg/day. The dose of CyA was adjusted to maintain trough levels between 100 and 200 ng/mL, and the appropriate dose was administered for at least six months. Granulocyte colony-stimulating factor (Filgrastim; Kirin, Tokyo, Japan) was administered intravenously or subcutaneously at 400 mg/m 2 for three months only to patients with very severe disease. 17 Response to IST was evaluated at six months after initiation of therapy. Complete response (CR) was defined as a neutrophil count more than 1.5×10 9 /L, a platelet count more than 100×10 9 /L, and a hemoglobin level more than 11.0 g/dL.17 Partial response (PR) was defined as a neutrophil count more than 0.5×10 9 /L, a platelet count more than 20×10 9 /L, and a hemoglobin level more than 8.0 g/dL in patients with severe or very severe AA, and as a neutrophil count more than 1.0×10 9 /L, a platelet count more than 30 ×10 9 /L, and a hemoglobin level more than 8.0 g/dL in patients with moderate AA.17 Overall response was defined as CR or PR at six months after IST. Statistical analysesParameters for univariate analyses to determine predictors of response to IST included age at diagnosis, sex, interval between diagnosis and treatment, etiology, severity of disease, white blood cell (WBC) count, neutrophil count, lymphocyte count, hemoglobin level, reticulocyte count, and platelet count. Pre-treatment laboratory values were defined as the lowest value without transfusions during the four weeks preceding IST. Continuous variables were divided into quartile categories, and these cut offs were used for categorical analysis. To evaluate correlations between these parameters and response, differences in continuous variables were analyzed using the Mann-Whitney U-test and differences in frequencies were tested using the χ 2 or Fisher's exact test. For multivariate analyses, logistic regression modeling was performed. Important covariates in the multivariate models were chosen using stepwise variable selection procedures. Values of P<0.05 were considered statistically significant. Results and DiscussionPatients' characteristics ...

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

“…When the two predictive parameters of ARC and ALC were combined, patients with higher baseline ANC and ARC had a response rate 40 % higher than those with lower baseline ANC and ARC (83 vs 41 %, p < 0.0001). 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].…”

“…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].…”

“…Pediatric patients reportedly have an approximately 70-80 % response rate; younger adult patients, 60-70 %; and adult patients >40-50 years of age, 50-60 % [11]. Yoshida et al [12] demonstrated men display better responses than women. This relationship was also observed in a European study in which a young female cohort demonstrated delayed recovery of bone marrow function following IST [13].…”

Diagnosis of acquired aplastic anemia

“…42 In children, lower WBC count (o2.0 Â 10 9 /L) was the most significant predictive marker of better response. 43 In patients receiving G-CSF, the lack of a neutrophil response (o0.5 Â 10 9 /L) by day 30 was associated with significantly lower response rate and survival. 44 Patients refractory to two consecutive courses of anti-thymocyte globulin (ATG) have a very low chance to respond to a third course of anti-thymocyte globulin, and may be suitable candidates for novel therapeutic options.…”

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia

“…Several conventional clinical parameters were proposed as predictors of a favorable prognosis, such as younger age, male gender, shorter interval between diagnosis and therapy, lower white blood cell count (WBC), higher absolute neutrophil count (ANC), higher absolute lymphocyte count (ALC), and higher absolute reticulocyte count (ARC). [5][6][7] However, their prognostic power is insufficient to affect clinical decision-making, and IST remains the first-line therapy for all AA patients lacking an HLA-matched sibling donor.…”