Enhanced marrow recovery by short preincubation of marrow allografts with human recombinant interleukin-3 and granulocyte-macrophage colony- stimulating factor

Abstract

We studied an alternative method of using hematopoietic growth factors (HGFs) to enhance hematopoietic recovery in patients undergoing bone marrow transplantation (BMT), by short in vitro preincubation. Twenty consecutive patients with leukemia received T-cell-depleted allografts using Campath-1G. Two thirds of the marrow was infused on the scheduled day of transplant and one third of the marrow following preincubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) on day 4. Engraftment parameters and duration of hospitalization were compared by actuarial analysis to those of 40 historical controls. Patients receiving the incubated boost had significantly faster platelet recovery (P = .017) and shorter hospitalization period (P = .001) when compared with the control subjects. Platelet count reached greater than 25 x 10(9)/L on day 17 (median) in the study group and on day 23 in the controls. The median duration of hospitalization was 20 and 36 days, respectively. In the early posttransplantation follow-up, two of four patients in the study group died as a result of graft rejection, while all 13 deaths in the control group resulted from complications associated with marrow suppression. We suggest that pretransplant in vitro activation of bone marrow cells with IL-3 and GM-CSF may prove to be an efficient method for enhancing marrow recovery after BMT.

Expansion of megakaryocyte progenitors from human umbilical cord blood using a new two‐step separation procedure

“…This method was effective in enriching Mk‐progenitor cells (CFU‐Mk), while simultaneously maintaining CD41 + , the CD34 + , erythroid and macrophage‐granulocyte progenitor cells. Increased numbers of committed Mk progenitors, which are short‐term engraftment cells, could decrease the period of thrombocytopenia following transplantation and prior to long‐term engraftment ( Naparstek et al , 1992 ). The gelatin/Ficoll‐Paque two‐step procedure also maintained the relative number of CD41 + , CD38 + cells and the CFU‐Mk was enhanced 34.3‐fold.…”

“…Ex vivo expansion of megakaryocyte (Mk) progenitor cells in CB could provide higher absolute numbers of these cells which are needed for faster platelet recovery after CBT. Ex vivo expanded Mks from peripheral blood (PB) and bone marrow (BM) have already been successfully transplanted in patients with malignant disorders ( Naparstek et al , 1992 ; Nagler et al , 1995 ; Bertolini et al , 1997 ).…”

Mimicking the haematopoietic niche microenvironment provides a novel strategy for expansion of haematopoietic and megakaryocyte‐progenitor cells from cord blood

“…Ex vivo expanded Mk were administered to patients receiving autologous peripheral blood transplant with no recorded toxicity (Bertolini et al , 1997). Pre‐incubation of bone marrow (BM) cells with interleukin 3 (IL‐3)+ granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) shortened platelet recovery following BM transplantation (Naparstek et al , 1992) and stimulated ex‐vivo expansion of Mk‐p (Nagler et al , 1995). Improved Mk‐p engraftment was reported in mice that received CB CD34 + cells cultured for 4 weeks with cytokine combinations and thrombopoietin (TPO) (Bruno et al , 2004).…”

Characterization of peripheral blood steady-state progenitor cells preserved in liquid culture conditions with or without GM-CSF and IL2

“…to the expansion of progen itor cells and recl ucccl the post-transplantation recovery period in mice (34). In acldition, a recent clinical stuc.ly inc.licated that the preincubation o f marrow allografts w ith IL3 or Gtl'i-CSF e nhanced the hemopoietic recovcry, rcclucing the time of severe cytopenia by approximately one wcck (35). Tn this study, as wcll as in others (28,36), PBPC products incubated wit h GM-CSF inclucecl cliffere ntiation towa rds the myclo icl series, as clemonstratecl by a rising count of cclls carrying the CD33, CD15, ancl HLA-DR rcce ptors.…”