Apheresis Cycles Research Articles

Soluble adhesion molecules (sICAM-1, sL-Selectin, sE-Selectin, sCD44) in healthy allogenic peripheral stem-cell donors primed with recombinant G-CSF

We analysed the effects of rhG-CSF (Amgen-Roche, USA) on serum changes of four soluble adhesion molecules (SAM) (sICAM-1, sL-Selectin, sE-Selectin and sCD44) in healthy peripheral allogeneic stem-cell transplantation donors and their correlation with acute GvHD and effect on engraftment kinetics. Serum SAM of 15 consecutive healthy HLA identical-sibling donors (median age 30 years, male:female ratio, 7:8) were monitored using a commercial ELISA Kit (Bender Med, Austria) prior to, on the day of first apheresis and 24 h after the cessation of rhG-CSF (10 microg/kg/day s.c. on 5 days) administration. Leukapheresis was started on the fifth day of rhG-CSF administration, using a continuous-flow blood separator (Cobe Spectra, COBE BCT, Inc, Lakewood, CO). Apheresis cycles were continued daily until a target of 4.0 x 10(6) CD34(+) cells/kg was reached. The results indicate a steady rise of sL-Selectin, sE-Selectin, and sCD44, but not of sICAM-1. Median number of mononuclear cells (MNC) and CD34(+) cells transfused were 7.7x 10(8)/kg and 6.0 x 10(6)/kg, respectively. There was a near-significant correlation between the sL-Selectin levels and CD34(+) cell yield (r = 0.49, 0.06). Median granulocyte and platelet engraftment days were 11 (10-18) and 12 (9-33), respectively. There was a significant inverse correlation between the CD34(+) cell dose and granulocyte levels (r = -0.68, p = 0.022), but not for platelet engraftment. The only correlation between SAM levels and engraftment was for sICAM-1 levels. Increasing sICAM-1 levels were a sign of prolonged neutropenia (r = 0.72, p = 0.011). No correlation between the apheresis day serum levels of adhesion molecules and acute GvHD was documented. Analysis of sICAM-1, sL-Selectin, sE-Selectin and sCD44 levels during allogeneic PBSC apheresis did not reveal any significant effect on engraftment and GvHD, except the correlation of sL-Selectin levels and collected CD34(+) cells. More research and data about the role of not only SAM levels, but also antigenic expression of SAM are required to enlighten leukocyte-endothelial cell interactions and egress of stem cells during G-CSF administration.

Combination chemotherapy with mitoguazon, ifosfamide, MTX, etoposide (MIME) and G-CSF can efficiently mobilize PBPC in patients with Hodgkin's and non-Hodgkin's lymphoma.

Many centers use CY and G-CSF to mobilize PBPC. In this study we explored whether a standard chemotherapy regimen consisting of mitoguazon, ifosfamide, MTX and etoposide (MIME) combined with G-CSF was capable of mobilizing PBPC in lymphoma patients. Twelve patients with Hodgkin's disease (HD) and 38 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3 to 20) of chemotherapy prior to mobilization. It was found that the optimal time of PBPC harvest was at days 12 and 13 after initiating the mobilization regimen. The median number of collected CD34+ cells per kg body weight was 7.1 x 10(6) (range 0.5-26.2). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 69% of the patients after one apheresis. When additional cycles of apheresis were done, only 6% failed to harvest this number of CD34+ cells. There was a statistically significant inverse correlation between the number of prior chemotherapy cycles and CD34+ cell yield (P = 0.003). No such association was found between CD34+ cell yield and prior radiotherapy. When MIME/G-CSF was compared with Dexa-BEAM/G-CSF, it was found that MIME/G-CSF tended to be more efficient in mobilizing PBPC in spite of being less myelotoxic. All patients transplanted with MIME/G-CSF mobilized PBPC had fast and sustained engraftment. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF can be successfully used to mobilize PBPC.

Peripheral Blood Stem Cell Transplantation: Critical Review

Autologous blood stem cell transplantations have been increasingly performed worldwide for almost ten years in place of autologous bone marrow transplantation and even of allogenic bone marrow transplantation. Several crucial issues were the subjects of impassioned controversies. Some of them are now satisfactorily answered while others still remain unresolved. First, it is now possible to conclude today that peripheral blood stem cells (PBSC) are undoubtedly capable of restoring short term hematopoiesis when reinfused after myeloablative therapy as well as even more rapidly than bone marrow stem cells, provided that they have been previously collected in sufficient amounts. On the opposite, it is still impossible to firmly prove that their very immature CD34+ cell subset, although in vitro functionally and phenotypically almost identical to their marrow counterpart, is actually responsible for sustained long term hematopoietic recovery, even if it is likely that these cells play a key role. Most of the time, using chemotherapy alone or a combination of chemotherapy and cytokine(s), mobilizing regimens allow collection of appropriate yields of PBSC with only a small number of apheresis cycles, provided that a sufficient number of residual stem cells remains to be stimulated, when, on the contrary, collection in steady-state is time-consuming and does not provide further accelerated post transplant hematopoietic recovery. It was initially hypothesized that PBSC could have a lower likelihood of tumoral contamination compared with bone marrow. In fact, biological as well as clinical data are discordant and probably depend largely on the type of disease, its evolutive history and its way of dissemination.(ABSTRACT TRUNCATED AT 250 WORDS)