Treatment of Hepatitis-Associated Aplastic Anemia with High Dose Cyclophosphamide.
Bibliographic record
Abstract
Abstract OBJECTIVE: Demonstrate that high dose cyclophosphamide (CY) induces durable hematologic remissions in patients with hepatitis-associated aplastic anemia (HAA). INTRODUCTION: HAA is a rare variant of aplastic anemia that accounts for 5% of cases. The hepatitis is seronegative and most often spontaneously resolves. The aplastic anemia that follows presents within a few months after the onset of hepatitis and is often fatal. The one other study that investigated treatment for HAA used antithymocyte globulin and cyclosporine, which induced remissions in 7 of 10 patients, with up to one year of follow-up. In that study, there were 3 deaths related to treatment failure and 1 relapse. High dose CY has induced durable remissions in severe aplastic anemia (SAA) and other autoimmune diseases, and we hypothesized that it could induce durable remissions in HAA as well. METHODS: Five patients (ages 6–17 years) with HAA and without a matched sibling BMT option were treated with CY (50 mg/kg/day IV x 4 days) plus mesna. Serology/PCR for HAV, HBV, HCV, EBV, and CMV were negative. All patients met criteria for very severe aplastic anemia pretreatment: bone marrow cellularity <25%, ANC <200/μL platelet count <20,000/μL, absolute reticulocyte count <60,000/μL. Infection prophylaxis consisted of trimethoprim/sulfamethoxazole, G-CSF, and fluconazole. RESULTS: All patients were transfusion dependent for erythrocytes and platelets prior to high dose CY. Other baseline and current values are shown in Table I. Four patients demonstrated hematopoietic recovery. Median time to ANC>500/μL was 51 days (range 44–369). Median time to transfusion independence for erythrocytes and platelets was 109 (range 57–679) and 160 (range 48–679) days, respectively. The 4 patients with hematopoietic responses are in remission up to 6 years after treatment without further immune suppression beyond high dose CY. Patient 2 met criteria for autoimmune hepatitis (AIH), and her AIH remains in remission, as well. Patient 5 had no hematopoietic response and died 3 months after BMT of multi-organ failure. CONCLUSIONS: High dose CY induced durable remissions in hepatitis-associated aplastic anemia in 4 of 5 patients based on follow-up from 1–6 years. Treatment failure led to one death in this series. The remission of HAA and AIH in one patient suggests that high dose CY may be an alternative and effective treatment for AIH, which is a disease characterized by long-term dependence on immunosuppression and recurrent relapses. Table I: Pre-Treatment and Current Patient Characteristics Age/Sex Follow Up ANC (cells/μL) ALT (U/L) Hgb (g/dL) Platelets (1000/μL) Nadir/Current Peak/Current Current Current * ANA titer >1:640 and anti-smooth muscle Ab titer 1:40. † Had no hematologic response and proceeded to unrelated BMT after 5 months 17/F 6 y 138 / 3430 1832 / 16 11.1 99 9/F* 2 y 178 / 2500 1186 / 11 13 140 14/M 16 mo 0 / 2380 2800 / 31 13.7 98 6/F 13 mo 0 / 669 2213 / 21 13.9 37 16/F 5 mo † 0 / † 3051 / † † †
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".