Improved Survival In Adults With Mixed-Phenotype Acute Leukemia Following Stem Cell Transplantation (SCT): A Single Centre Experience
Bibliographic record
Abstract
Abstract Background Biphenotypic acute leukemia (BAL) is a rare subtype of leukemia accounting for 1% to 4% of all acute leukemias. They are associated with unfavorable outcome especially in adult population when treated with standard chemotherapy alone. Management issues like type of induction therapy, consolidation strategies, and role of high dose chemotherapy with stem cell transplantation remain unclear. Methods A retrospective review of 28 patients (pts) with BAL who were treated in Vancouver between 1984 and 2012 was performed. Diagnoses were confirmed according to WHO 2008 guidelines by two hematopathologists who independently reviewed morphology, immunophenotyping and in few cases immunohistochemistry. Kaplan-Meier estimates were utilized for event free survival (EFS) and overall survival (OAS). Characteristics There were 23 males and 5 females with a median age of 47 (range 17 - 75) years. Median white cell count (WCC) at presentation was 7.7 x 109(range: 0.9 to 192x109)/L. Immunophenotyping revealed “Myeloid + B-lymphoid” pattern in 13 pts (46.4%), “Myeloid + T-lymphoid” pattern in 13 pts (46.4%), “Myeloid + B-lymphoid + T-lymphoid” pattern in 1 pt (3.6%) and “T-lymphoid + B-lymhoid” pattern in 1 pt (3.6%). Cytogenetic studies revealed Normal karyotype in 6 pts (21.43%), complex karyotype in 6 pts (21.43%), Philadelphia chromosome positivity in 3 pts (10.71%), MLL rearrangement in 1 pt (3.57%) and other chromosomal abnormalities in 9 pts (32.14%). Cytogenetic studies failed in 2 pts (7.14%) and no data was available in 1 pt (3.57%). Induction therapy was of AML type in 5 pts (17.9%), ALL type in 8 pts (28.6%), and combination of AML and ALL type in 15 pts (53.6%), and 2 of the 3 pts with Philadelphia positivity also received imatinib (one patient was treated in the pre-Imatinib era) with induction chemotherapy. Twenty (71.43%) pts achieved complete remission (CR), 16 with one cycle and 4 with two cycles. Twelve pts went on to receive high dose chemotherapy with SCT. Stem cell source was autologous in 2 pts (16.7%), related donor in 3 pts (25%), unrelated donor in 6 pts (50%), and unrelated cord blood in 1 pt (8.3%). Eleven of 12 pts were in first CR and one was in second CR before SCT. Conditioning chemotherapy was TBI-based in 7 pts and busulfan based in 5 pts. Results ALL treatment induced a remission in 45%, AML therapy in 0% and 53% responded to combination therapy. EFS and OAS estimates for all 28 patients at 15 years were 29% (95% CI 13% to 48%) and 40% (95% CI 21% to 58%) respectively. Patients receiving high dose chemotherapy and SCT had significantly improved OAS of 63% (95% CI 29% to 85%) vs. 23% (95%CI 6% to 46%) for those receiving only chemotherapy (P = .019). OAS for pts with presenting WCC of <30x109 was significantly better compared to pts with presenting WCC of >60x109 (54% vs. 0%, p = .039).”Myeloid + B lymphoid” group had better OAS estimates compared to “Myeloid + T- lymphoid” group (59% vs. 29% respectively, but not statistically significant, p= 0.1135). Type of induction chemotherapy, and age at diagnosis were not statistically significant outcome predictors. Conclusion Although a small sample size, this study would suggest that adult patients with BAL who achieve a CR with standard chemotherapy should be considered for high dose chemotherapy and stem cell transplantation. This modality of treatment gives them the greatest probability of long term overall survival. Disclosures: Sutherland: Celgene: Honoraria; Janssen : Honoraria; Novartis: Honoraria. Toze:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".