Cryopreserved Allogeneic Peripheral Blood Stem Cells Result in Outcome Equivalent to Those of Fresh Infusions Enabling Rational Scheduling of Donations,
Bibliographic record
Abstract
Abstract Abstract 4052 Introduction: Donor stem cells are traditionally infused fresh into recipients in the setting of allogeneic hematopoietic stem cell transplantation (allo-SCT). In this study, we investigated outcomes of 133 sibling allografts using cryopreserved peripheral blood stem cells. We demonstrate that cryopreservation did not have a negative impact on engraftment when compared to data from the IBMTR/EBMT, Seattle and the Canadian registry studies. Non-relapse mortality (NRM) and overall survival (OS) were within acceptable limits. Patients and Methods: We identified all recipients of HLA-matched sibling peripheral stem cells cryopreserved for a minimum of 7 days, who underwent allo-SCT at Hammersmith Hospital from January 1998 until May 2011 (n = 133). The median age at allo-SCT of 78 (59 %) males and 55 (41 %) females was 48 (17 – 65) yrs. Thirty-five (26 %) were transplanted for CML (including accelerated and blast phase), 42 (31 %) for AML, 11 (8 %) for ALL, 14 (11 %) for myeloma and 13 (10%) for other causes. Fifty-six (42 %) had myeloablative and 77 (58 %) had reduced intensity conditioning, with 23 (17 %) having in vivo T-cell depletion with monoclonal anti-CD52 antibody (alemtuzumab). Using validated institutional protocols hematopoietic progenitor cell collections were cryopreserved on the day of collection or on following morning. Cells are were mixed with 10 % v/v dimethyl sulfoxide, frozen to -−00°C at a controlled rate and then transferred to vapor phase liquid nitrogen ≤ −150°C. Thawing and infusion of cells were performed in accordance with a standard protocol defining thawing temperature and the maximum time between thawing and infusion. Median CD-34+ cell dose infused was 9.83 × 106/kg (range 2.4 – 33 × 106/kg). All cryopreserved peripheral blood stem cell collections were infused into the recipients. Engraftment was defined as a peripheral absolute neutrophil count (ANC) of 0.5 × 109/L for 2 successive days and platelet count of > 50 × 109/L for 2 consecutive days, both without support. G-CSF was used only in delayed neutrophil engraftment (> 30 days). Results: Overall 125 (93 %) achieved neutrophil engraftment and median time to engraftment was 19 (range 10 – 42) days. Delayed neutrophil engraftment (>30 days) was present in 4 patients. Results are comparable to the registry data which showed neutrophil engraftment in a median of 14 – 19 days (Table 1). Cumulative probability of achieving ANC > of 0.5 × 109/L for the whole cohort was 94 % (88 – 95). Eight of the 133 patients who died early (< day 30) failed to achieve neutrophil engraftment prior to death. The causes of death were sepsis (n = 6), myocardial ischemia (n = 1) and renal failure (n = 1).Three recovered counts with G-CSF and one patient required stem cell rescue. One hundred and thirteen patients (84 %) recovered platelets to >50 × 109/L within a median time of 21 (range 0 – 240) days, which again is similar to registry data as shown in table 1. The cumulative probability of achieving platelets of 50 × 109/L was 84 % (77 – 88). Twenty patients (16 %) failed to achieve this threshold and causes were multiple. There was no association between CD34+ cell doses infused and delayed or non engraftment of platelets. The incidence of acute and chronic GvHD were 44 % (grade II-IV GvHD 31 %) and 30 % (50 % extensive) respectively. Day 100 NRM was 23 % and OS at 3 years was 50 %. Conclusion: This study provides evidence that cryopreservation and subsequent infusion of peripheral blood stem cell harvests is safe, ensures durable engraftment and is comparable to fresh stem cell infusions (Table 1). We do not routinely use growth factors to aid count recovery and as such the time to engraftment data is consistent. Cryopreservation importantly allows for flexibility in arranging admissions and scheduling regimens for both the donors and the transplant units. Although not observed in our cohort, there is a theoretical risk of not utilizing the cryopreserved cells, thus unnecessarily harvesting donors. One way to circumvent this possibility is by timing the collection close to the transplant. 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 | 0.001 | 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) | 0.002 | 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".