Langerhans Cell Histiocytosis with Hematological Dysfunction, Refractory to Standard Therapy Could Be Cured by an Association of 2-CdA and Ara-C: Concordant Results from the Observational Survey of Treated Patients and from a Nation Wide Registry.
Bibliographic record
Abstract
Abstract In Children’s Langerhans cell histiocytosis, hematological dysfunction refractory to standard regimen, is the major cause of death until recently. In 2005, (Eur J Cancer, Bernard F et al, 2005) we have reported the results of a pilot study of 2-CdA and Ara-C in this extremely rare subset of patients. Among 10 patients enrolled between 1996 and 2004 (group 1), seven were cured, but three died, two of toxicity, and one after subsequent bone marrow transplantation. We report here A) the results of the 9 additional patients treated in France between mid 2004 and july 2007 (group 2) and B) the results of the national registry which had collected at the national level all cases of LCH in france since 1983. A) The group 2 comprised 9 patients who have all received at least two courses of Ara-C (1000 mg/m2/d) and 2-CdA (9 mg/m2/d) administered for 5 days. Maintenance therapy usually involved 6 courses of 2-CdA (5mg/m2 for 3 days every 3 weeks). Group 2 was comparable to group 1 for median diagnosis age (group 1: 0.78 years vs group 2: 0.73 years), as well as the number of organs involved. The delay between LCH diagnosis and 2-CdA Ara-C onset was shorter in the group 2 (group 1: 0.98 years- group 2: 0.35 years). The initial regimen to treat LCH was the same in the two groups (Vinblastine + steroid +- Methotrexate = LCH III protocol). Group 1 had received several second line therapies before 2-CdA Ara-C, while group 2 had received only the 2-Cda Ara-C as a second line therapy. Grade IV WHO haematological toxicities were observed in all patients, but no toxic death was observed in the group 2. One patient in group 2 underwent a 2-CdA overdose (injection at 10-fold the dose) but no major side effect was observed and latter the protocol was completed. After 2 courses, a decrease in disease activity was observed in all patients, but none had achieved a complete remission status after 2 courses. One patient had received a subsequent HSCT with an attenuated conditioning regimen with a very short hematological recovery at day 15, while the other patients had received only standard chemotherapy regimen as maintenance. Complete remission was achieved in the 8 assessable patients (including the patient who had received HSCT) and one patient had still an active disease but only 2 months after 2-Cda Arac onset. B) In the national French LCH register, 103 cases with hematological dysfunction, among 827 patients (<18 years), were registered from 1983 to 2007. In the same period, 45 deaths were observed, 34 (75%) with haematological dysfunction. In the latter group, the death rate dramatically decreased since the recommendation of 2-Cda Arac as salvage therapy for patients haematological dysfunction refractory to standard chemotherapy in France (1996) as 28 deaths were observed in the 54 patients diagnosed before 1996 (51%) and 6 among 49 patients since 1996 (12%) (p<0.001). In conclusion, 2-CdA and Ara-C combined chemotherapy has major activity to treat refractory LCH with haematological dysfunction, despite a high toxicity. This promising results warrant confirmation in the phase II open labelled study LCHS2005, officially open in France, and in Canada and in few centers in USA.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".