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Immunosuppressive therapy for pediatric aplastic anemia
was noted in 55 (39.3%). In most cases, the clone size was small [interquartile range (IQR): 0-0.12%]. Only 5 patients had PNH clones larger than 10% (range: 12.56-28.4%) in the granulocyte lineage and none had clinically evident hemolysis or thrombosis at diagnosis.
The most commonly investigated inherited BM failure syndromes at diagnosis were Fanconi anemia, Shwachman-Diamond syndrome, and dyskeratosis con- genita. Fanconi anemia screening was negative for 292 patients (93%), 18 patients were not tested, and results were not available for four subjects. Genetic testing for Shwachman-Diamond syndrome was available for 46 patients (14.6%); all of these were negative. Perhaps reflecting the evolution of understanding the role of dyskeratosis congenita in BM failure over the past five years, telomere length was assessed at the time of diagno- sis in only 115 patients (36.6%) and a report of a clinical telomere flow-FISH test was available for 93 patients (29.6%). No patient exhibited a pattern suspicious for a primary telomere disorder (telomeres <1st percentile in at least 3 different lymphocyte subsets).13 However, telomere lengths <1st percentile were found in total lymphocytes in six patients, of whom only two had a complete 6-panel analysis.
The current diagnostic criteria for SAA includes an ARC (absolute reticulocyte count) of <20-60x109/L.12,14,15 Many institutions relied on hemoglobin (Hb) rather than the ARC as a more clinically relevant indicator of ery- throid hypoplasia to inform diagnosis and treatment deci-
Figure 1. Correlation between absolute reticulocyte count and hemoglobin at diagnosis. Absolute reticulocyte counts <100x109/L (n=231) were plotted against the hemoglobin at diagnosis. CI: Confidence Interval.
Table 5. Response outcome in each treatment group.
sions. Comparison of ARC versus Hb for the 231 subjects with ARC <100 revealed a lack of concordance [(estimat- ed Pearson correlation coefficient of 0.15 (95%CI: 0.02, 0.27)] between the commonly utilized diagnostic criteria of ARC of <60 x109/L and significant anemia defined as Hb <8 g/dL (Figure 1). A subset of patients meeting ARC criteria of ARC <60 x109/L had Hb >8 g/dL (12.7%, 28 of 220), and conversely, some patients who did not meet diagnostic criteria for ARC had Hb levels <8 g/dL (74%, 26 of 35).
Treatment
Treatment groups are outlined in Table 3. The majority of patients (n=264) received hATG plus CyA. Of these subjects, one patient received hATG but switched to rab- bit ATG (rATG) due to an anaphylactic reaction. Overall, the demographics of the hATG/CyA population was sim- ilar to that of the entire group (Tables 1-3). The small num- ber of subjects in groups treated with alternative IST regi- mens limited intergroup comparisons, and so only out- comes of the entire population and that of the hATG/CyA group were analyzed.
Of the 282 subjects who were treated with hATG,187 (71%) received 40 mg/kg/day for four days, 77 were dosed with a different regimen containing about the same total dose of hATG, and in 18 the dose was not available. CyA target trough levels were variable (100-400), with the majority 200-400. Following treatment with hATG/CyA, data regarding the cyclosporine taper were available for 194 patients. CyA was discontinued by six months for 13 subjects, between 6-12 months for 40 sub- jects, between 12-18 months for 34 subjects, between 18- 24 months for 37 subjects, and after two years for 34 sub- jects. CyA was not discontinued at last follow up for 36 subjects.
Median time from diagnosis to treatment for all subjects was 24 days with an IQR of 12-40 days for the entire
Table 4. Best response to immunosuppressive therapy.
Response All treatments hATG/CyA N%N%
CR 189 60.2
VGPR 23 7.3
PR 10 3.2
NR 79 25.2
NE 13 4.1
Total 314 100
158 59.8
22 8.3
8 3
66 25
10 3.8
264 100
CR: complete response; VGPR: very good partial response; PR: partial response; NR: no response; NE: not evaluable.
Response Outcome
Objective Response (CR+VGPR+PR)
Deep Response (CR+VGPR)
Complete Response (CR)
Treatment Number of responses
All 222 hATG/CyA 188 All 212 hATG/CyA 180 All 189 hATG/CyA 158
Response Rate (%)
70.7 71.2 67.5 68.2 60.2 59.8
95% CI*
65.3, 75.7 65.3, 76.6 62.0, 72.7 62.2, 73.8 54.5, 65.7 53.7, 65.8
*95% exact binomial Confidence Interval.
haematologica | 2019; 104(10)
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