Tandem Autologous-Allogeneic Nonmyeloablative Sibling Transplant in Relapsed Follicular Lymphoma Leads to Impressive Progression Free Survival with Minimal Toxicity.
Bibliographic record
Abstract
Abstract Abstract 50 High dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been shown to prolong progression free survival (PFS) as well as overall survival (OS) in patients (pts) with relapsed follicular lymphoma (FL). However, ASCT is usually not considered curative. Myeloablative allogeneic transplant has produced long term PFS in a subgroup of pts but is hampered by significant transplant related mortality (TRM). Reduced intensity transplant has less TRM but reports suggest a higher relapse rate. We therefore hypothesized that a tandem strategy consisting of ASCT followed by nonmyeloablative allogeneic transplant (NMT) would mimic a myeloablative allogeneic transplant without the associated early toxicity. We initiated such a prospective protocol for pts with relapsed FL in 2003. Patients underwent ASCT with a chemotherapy based conditioning regimen; 3 months post ASCT, pts with a 6/6 related donor received an outpatient NMT with 5 days of fludarabine 30 mg/m2/d and cyclophosphamide 300 mg/m2/d followed by infusion of ≥4×106 donor CD34+ cells/kg. GVHD prophylaxis, selected to take advantage of the low incidence of acute and the putative protective effect of chronic GVHD (as we have previously published in BBMT 2009 Aug;15(8):919), consisted of tacrolimus 3 mg bid started on day (D)-8 to achieve levels of 10–15 nmol/L then tapered off by D+100 and mycophenolate mofetil 1 g bid from D+2 to D+50. Between 4/2003 and 10/2008, 27 pts (M/F: 19/8) underwent tandem transplant, including 25 with FL and 2 with histology compatible with either FL or marginal zone lymphoma; 6/27 had histological progression towards an aggressive lymphoma. Median age was 49 years (range 34–65). The pts had previously been treated with a median of 3 lines of therapy (range 2–6). Median time from diagnosis to transplant was 34 months (range 14–131); 8 patients had never been exposed to rituximab. Disease status prior to ASCT was: 8 CR, 14 PR and 5 refractory. Conditioning chemotherapy for ASCT was: BEAC (n=14) and BEAM (n=13). 23 pts received peripheral blood stem cells and 4 received bone marrow for their ASCT. 2 pts received radiotherapy after ASCT to sites of previously bulky disease. Median time between ASCT and NMT was 133 days (range: 75–285). Pre NMT disease status was: 14 CR, 8 PR, 3 refractory, and 2 unknown. Median number of CD34+ cells/kg infused for NMT was 8.2 ×106 (range 3.2–29.2). Engraftment was prompt in all pts. 5 pts (18%) developed acute GVHD: 1 grade II and 4 grade III (2 classic acute and 3 delayed onset). Overall, 18 (67%) pts developed extensive chronic GVHD requiring treatment. Disease status at last follow up was: 22 CR and 5 unconfirmed CR. To date, there has been no disease progression and only 1 patient has died from GVHD at +11 months. With a median follow-up of 34 months (range 11–70) OS and PFS are both 96% at 3 and 5 years. In conclusion: 1) ASCT followed by sibling NMT for relapsed FL appears to be safe and well tolerated. 2) Disease response and PFS are excellent even in refractory and transformed cases of FL. 3) This novel approach warrants further investigation in larger prospective studies. Disclosures: No relevant conflicts of interest to declare.
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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".