Abstract
Importance of the viability of stem cell grafts on transplantation outcome is not fully explored; however, presumably better viability results in better posttransplantation disease course. The results of the past eight years gained in our center with autologous hemopoietic stem cell transplantation were analysed, mainly in multiple myeloma (MM), Non-Hodgkin lymphoma (NHL), Hodgkin disease (HD) and some autoimmune diseases.
Right before the beginning of the transplantation procedure a small aliquot of the cell products were transferred to a haematological cell counter (Abacus Junior, Diatron, Austria), CD34+ cell counts were established by immunophenotyping, and to assess the global MNC viability trypan blue dye exclusion was used (European Pharmacopoeia 7.0; 01/2008:20729). A retrospective survey of our regular autologous transplant cases and their follow up was analysed in the so called poor viability cases, as opposed to the so called better viability cohort. Our arbitrary poor viability cut off point was less than 81% global MNC viability. To characterize the transplantation outcome the following parameters were used: duration of aplasia, length of neutrophil and platelet engraftment, post transplantation overall survival data. We could not rely upon standard progression free survival asssessment and median survival analysis, due to the broad range of the timing of the interventions (including quite recent cases, too) and also due to changes in therapy along with the new innovative agents used predominantly more recently.
We performed 358 autologous transplants between 2006 and June 2013. Considering our viability cut-off point we divided our patients into good viability graft group (n=306) and into poor viability graft group (n=52). The poor viability grafts contained significantly lower stem cells, but we did not identify how this viability data affected the rather mixed other cell lines of the MNC complex.
There were no significant differences observed regarding the duration of aplasia, neutrophil and platelet engraftment times between two groups (Table 2).Table 1Main graft parameters in two patient group (Mean±SD)Low viability graftGood viability graftP valueMNC (×108/bw)4.132±3.6894.969±5.881P=0.3215CD34+ (×106/bw)3.554±2.2245.527±2.339P<0.001Table 2Post transplantation parameters in the poor viability graft groupDg<0.5 G/L WBC(day)<20 G/L PLT(day)Aplasia(day)Engraftment time(>1.0 G/L WBC)HD7.69.84.610.3NHL9.210.25.210.2MM4.83.82.910.6
There was no correlation between low viability CD34+ cell number and survival time if analysed independently of the diagnosis. No more severe neutropenic infections (grade III-IV) were registered in the low viability graft cohort compared to the good viability patients. Interestingly 7 out of 11 patients autotransplanted with autoimmune diseases had low viability cell product and this subgroup mortality was better, i.e. 29% compared the good viability cases (less T cells contributing to autoimmunity?). However, the cumulative mortality of the hematological patients was associated with excess mortality in our low viability group (Table 3).Table 3Comparison of graft and mortality of transplantation according to diagnostic subgroups with poor or good graft viability (MNC (×108/bw) and CD34+ (×106/bw); Mean±SD)DgParameterLow viability graftGood viability graftPHDn1238MNC3.625±2.2324.989±4.4700.3161CD34+4.008±2.2205.818±3.3890.09mortality33%24%NHLn15104MNC6.700±5.1355.274±4.4960.2616CD34+3.013±1.5815.145±2.1790.0004mortality47%20%MMn17156MNC2.859±2.3194.797±6.9570.2563CD34+2.971±1.4995.626±2.073<0.0001mortality53%23%
Poor viability, defined arbitrarily as 80% or less graft MNC trypan blue stain assay resulted in worse outcome in our retrospective analysis of autografted multiple myeloma, Hodgkin and non-Hodgkin lymphoma cases. The corrected CD34+ count seemed to be less important, as the length of aplasia, engraftment period, severe neutropenic infections, etc. seems to be identical with the good viability cohort results. Our results are suggesting that the diminished viability of non CD34+ components of the graft MNC (most likely T cells) might influence the long-term outcome of autologous transplant patients. This hypothesis needs further support, i.e. well planned, prospective, comprehensive analysis, focusing on the autografted T lymphocytes.
Disclosures:
No relevant conflicts of interest to declare.
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