Characterization of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro.

Summary:CD90 or Thy-1 is an antigen co-expressed with CD34 ؉ on putative immature hematopoietic stem cells. Peak mobilization of CD34 ؉ 90 ؉ cells into the blood occurs a few days earlier than peak mobilization of total CD34 ؉ cells. Because it is not known which cell type best correlates with engraftment, the optimal timing of apheresis remains unclear. The purpose of the study was to determine if the CD34 ؉ 90 ؉ cell dose predicts engraftment of autologous blood stem cells independent of the total CD34 ؉ cell dose/kg, the dose of other CD34 ؉ cell subsets (CD34 ؉ 33 ؊ , CD34 ؉ 38 ؊ , CD34 ؉ 41 ؉ ), or various clinical factors. Data were analyzed on 125 consecutive patients ranging in age from 19 to 66 years (median 46) who underwent autologous blood stem cell transplantation (ABSCT) for breast cancer (54), lymphoma (59), or other malignancies (12). By univariate analysis, neutrophil (у0.5 ؋ 10 9 /l) and platelet (у20 ؋ 10 9 /l or у100 ؋ 10 9 /l) engraftment correlated better with the total CD34 ؉ cell dose than with the CD34 ؉ 90 ؉ cell subset. Using Cox proportional hazards models, factors independently associated with both neutrophil engraftment (у0.5 ؋ 10 9 /l) and platelet engraftment (у20 ؋ 10 9 /l and у100 ؋ 10 9 /l) were higher total CD34 ؉ dose/kg and high-dose regimen (melphalan-containing slower than other regimens). In conclusion, the total CD34 ؉ dose/kg was a better predictor of hematopoietic engraftment following ABSCT than the dose of any CD34 ؉ subset, including CD34 ؉ 90 ؉ cells. Apheresis should continue to be timed according to peak CD34 ؉ levels. Bone Marrow Transplantation (2000) 25, 435-440. Keywords: hematopoietic stem cell transplantation; hematopoietic stem cells A prerequisite for safely treating patients with high-dose chemotherapy and autologous blood stem cell transplantation (ABSCT) is the ability to accurately predict hematopoietic recovery. At present, the marker most commonly utilized for this purpose is the total CD34 ϩ cell dose/kg. [1][2][3] Within the CD34 ϩ cell population, however,

Section: Hematopoietic Engraftment After Absctmentioning

confidence: 99%

mentioning

confidence: 99%

The CD34+90+ cell dose does not predict early engraftment of autologous blood stem cells as well as the total CD34+ cell dose

Guo

Luider

et al. 2000

“…All colony types were identified according to previously reported criteria. 11 Values for the total clonogenic cell content of every fraction of cells assayed were extrapolated by multiplying the number of colonies counted by the number of cells in every fraction and dividing by the number of cells plated per ml.…”

Section: Hematopoietic Progenitor Cell Assaysmentioning

confidence: 99%

Rapid engraftment after allogeneic transplantation using CD34-enriched marrow cells

Cornetta

Gharpure

Mills

et al. 1998

Summary:Bone marrow cells expressing the surface antigen CD34 comprise approximately 1% of harvested marrow and are highly enriched for marrow progenitor cells, including the cells believed to be responsible for long-term engraftment following bone marrow transplantation (BMT). Selection of CD34-expressing cells was applied in allogeneic BMT (alloBMT) to decrease the number of T lymphocytes in the infused marrow in an attempt to prevent severe graft-versus-host disease (GVHD). We report 14 patients who underwent HLA-identical sibling-matched alloBMT with marrow-enriched for CD34 cells using the Isolex 300 SA device. Patients received total body irradiation, thiotepa, cyclophosphamide, antithymocyte globulin and methylprednisolone prior to marrow infusion. No post-transplantation immunosuppressive therapy was given except for a 5-week course of steroids. The purity of the infused marrow was 64.9 ؎ 6.0% (mean ؎ s.e.m.) CD34-positive cells and patients received a mean of 1.24 ؎ 0.21 ؋ 10 6 CD34 cells/kg. A mean of 9.4 ؎ 1.7 ؋ 10 4 CD3 T cells/kg were present in the CD34-enriched product, representing a 2.7 ؎ 0.1 log depletion. There were no graft rejections and patients achieved a sustained absolute granulocyte count of Ͼ500 in a median of 10.5 days and a sustained platelet engraftment of Ͼ20 000 untransfused in a median of 27 days. Patients were discharged a median of 21.5 days after marrow infusion. There were no instances of grade III or IV graft-versus-host disease (GVHD) and no unexpected adverse events during the transplant hospitalization. With a median follow-up of 12 months, the estimated 100 day survival is 86 ؎ 9%. CD34 selection in alloBMT permits rapid engraftment without unanticipated toxicities. Keywords: CD34 selection; engraftment; allogeneic transplantationThe marrow infused during bone marrow transplantation (BMT) contains a wide variety of cells, the vast majority

“…4 Further characterization of the CD34 + cell population by flow cytometry can identify multipotent progenitor cells more accurately by the expression of CD45Ro, 5 and by the lack of expression of CD38, 6 CD33, 7 CD13, 8 and HLA-DR. 8,9 Committed progenitor cells express CD34 along with antigens associated either with myeloid (CD33, CD13), 10 erythroid (CD71), 11 lymphoid (CD7, CD19), 12 or megakaryocytic lineage (CD41, CD61). 13,14 The role of these various CD34 + subsets in predicting the reconstitutive capacity of an autologous blood stem cell graft, however, is not well defined.…”

mentioning

confidence: 99%

Factors predicting engraftment of autologous blood stem cells: CD34+ subsets inferior to the total CD34+ cell dose

Stewart

Guo

Luider

et al. 1999

Summary:Data were analyzed on 178 consecutive patients (median age 43 years) who underwent autologous blood stem cell transplantation (ABSCT) at a single institution to determine if CD34 + subsets (CD34 + 38 − , CD34 + 33 − , CD34 + 33 + , CD34 + 41 + ) or various clinical factors affect hematopoietic engraftment independent of the total CD34 + cell dose/kg. Using Cox proportional hazards models, the factors independently associated with rapid neutrophil engraftment were higher CD34 + dose/kg, use of G-CSF post-ABSCT, and conditioning regimen (single-agent melphalan ± TBI slower). Factors independently associated with rapid platelet engraftment were higher CD34 + cell dose/kg, higher ratio of CD34 + 33 − /total CD34 + cells infused, conditioning regimen (mitoxantrone, vinblastine, cyclophosphamide faster), and no CD34 + cell selection of the autograft. The CD34 + cell selection process seemed to deplete CD34 + 41 + cells to a greater extent than total CD34 + cells which may explain our observation that it resulted in slower platelet engraftment. In conclusion, the total CD34 + dose/kg was a better predictor of hematopoietic engraftment following ABSCT than the dose of any CD34 + subset. Platelet engraftment, however, was also influenced by the ratio of CD34 + 33 − /total CD34 + cells for unmanipulated autografts, and possibly by the CD34 + 41 + dose for autografts manipulated by CD34 + selection. The use of CD34 + subsets requires further investigation in predicting engraftment of autografts which undergo ex vivo manipulation.