Patients eligible for transplant

Autologous transplantation using a simple method to store peripheral blood stem cells

Autologous stem cell transplantation (ASCT) is the standard of care for younger (< 65-70) and/or fitter multiple myeloma (MM) patients (pts). Briefly, following an induction therapy, stem cells (SCs) are collected from the patient’s peripheral blood (PB) and are usually stored in liquid nitrogen (-196oC) in a solution that contains the cryoprotectant dimethyl sulfoxide (DMSO). After receiving high-dose chemotherapy with melphalan, pts undergo ASCT using the stored PBSCs.

Storing the SCs in liquid nitrogen requires expensive equipment and well-trained personnel. In addition, the use of DMSO can cause some mild or severe adverse reactions in some pts. Maria Cecilia Borges Bittencourt, from the Department of Hematology, University of Sao Paulo, Sao Paulo, Brazil, and collaborators, examined the efficacy and safety of ASCT using PBSC that were either cryopreserved in liquid nitrogen (CRYO) or kept in liquid state for up to 48 hours at 4oC (non-CRYO) in blood bank refrigerators. The primary endpoint of the trial was neutrophil engraftment (NE). Secondary endpoints included early transplantation related mortality (TRM), infection, infusion-related complications, and costs. The results of the study were published in the journal Bone Marrow Transplantation in August 2018.

Data is given as CRYO vs non-CRYO

Study Design:
  • SC mobilization = G-CSF or cyclophosphamide + G-CSF or Plerixafor + G-CSF vs G-CSF
  • Minimum yield of cells prior to ASCT = 2 x 106 CD34+ cells/kg
  • Dose of melphalan = 200 mg/m2, or 140 mg/m2 if pts had chronic renal failure or heart failure
  • Medication prior to infusion = diphenhydramine, hydrocortisone, and dipyrone vs none
  • On day 5 after ASCT (+5) = daily dose of 300 mcg of G-CSF until neutrophil recovery
  • NE = Time from infusion to the first of three consecutive days with absolute neutrophil count of at least 500/mm3
  • Graft failure = No neutrophil recovery until 28 days after transplantation
  • Early TRM = death related to ASCT on the first 30 days
  • Infection = Examined from infusion until NE
  • Adverse events (AEs) = Infusion-related complications to DMSO vs unexpected symptoms 24 hours after infusion
Key Data:
  • Number of pts with CRYO vs non-CRYO ASCT = 63 vs 45
  • Gender (Male) = 40 vs 29
  • Age (± SD) = 55.65 (± 8.53) vs 82 (± 8.55)
  • Median dose of cells (CD34+ x 10/kg) = 4.0 (interquartile range [IQR], 3.2-5.1) vs 3.5 (IQR, 2.8-4.6), P = 0.04
  • Median number of days of NE = 13 (IQR, 12-15) vs 10 (IQR, 10-11) (P < 0.0001)
  • Graft failure occurred in one pt (CRYO group) who achieved NE at day 35 after ASCT (+35)
  • Early TMR = 5% (3 pts) vs 2% (1 pt)
  • Infection = 41% vs 29%, P = 0.23
  • AEs = 15 vs 5
  • Cost analysis for one unit = $1300 vs $300
Conclusions

This study reveals that non-CRYO ASCT is non-inferior to CRYO ASCT and can be used effectively in multiple myeloma. NE was achieved earlier in the non-CRYO group compared to the CRYO group, and the number of infections was similar between the two groups. Non-CRYO offers the advantage of being more cost-effective, which provides a great benefit for countries with limited cryopreservation resources and budget. Moreover, in the non-CRYO procedure pts do not develop AEs related to the presence of DMSO. A drawback of the non-CRYO method is that SCs are not available for a second ASCT. The findings of this study are in accordance with the fact that SCs remain viable for up to 3-5 days when stored in liquid state in blood bank refrigerators at 1-6o C.

References

Bittencourt M.C.B. et al. Cryopreserved versus non-cryopreserved peripheral blood stem cells for autologous transplantation after high-dose Melphalan in multiple myeloma: comparative analysis. Bone Marrow Transplantation. 2018 Aug 14. DOI:10.1038/s41409-018-0250-1. [Epub ahead of print]

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