Immunological reconstitution and correlation of circulating serum inflammatory mediators/cytokines with the incidence of acute graft-versus-host disease during the first 100 days following unrelated umbilical cord blood transplantation

Summary:Umbilical cord blood (UCB), bone marrow (BM) and mobilized peripheral blood (mPB) are used as sources of hematopoietic stem cells for transplantation. The NOD/SCID mouse model was used to compare the lineage-specific repopulating potential of CD34 + cells derived from these sources. Six to 8 weeks after transplantation, blood, BM, spleen, liver and thymus, were harvested, and analyzed by flow cytometry using CD34, CD45, myeloid, and lymphoid lineage-specific antibodies. Fifty percent engraftment of human cells in bone marrow of mice was estimated to be reached with 0.55 × 10 6 CD34 + UCB cells or with 7.9 × 10 6 CD34 + cells from adult sources, illustrating a 10-fold superiority of UCB CD34 + cells to engraft NOD/SCID mice. Lineagespecific characterization of engrafted human cells showed that the high engraftment potential of CD34 + cells from UCB was due to a preferential B cell development (2-81%). In contrast, comparable percentages of myeloid cells were found following transplantation of CD34 + cells from UCB, BM and mPB (1-38%), and occurred at significant levels only at relatively high doses. Since the CD34 content of UCB transplants is usually at least one log lower than of transplant from adult sources, these results correspond to the clinical findings with UCB transplantation showing a relatively high overall engraftment, but delayed myeloid recovery. blood (mPB), and umbilical cord blood (UCB). The HPC source used for an individual patient may depend on the availability of the graft, the disease and the age of the patient, and the risks of complications after the transplant. For instance, transplantation with a mPB graft has been shown to result in more rapid recovery of granulocytes and platelets than BM transplantation, but is associated with a higher incidence of chronic graft-versus-host disease (GVHD). [2][3][4] In contrast, UCB transplantations have been reported to be accompanied by a relatively low incidence and severity of GVHD, but are associated with delayed hematopoietic recovery. 5,6 In part, the relatively slow speed of engraftment following UCB transplantation is thought to be due to the limited numbers of HSC that can be transplanted. The limited volume of UCB that can be obtained from a single harvest results in a graft usually containing at least one log fewer CD34 + cells than a BM graft. 6,7 However, qualitative differences in the CD34 + cell fraction from the various sources of HSC may also influence the recovery after transplantation. [8][9][10][11][12][13][14] The CD34 + CD38 Ϫ cell population from UCB, containing the most primitive cells essential for engraftment, showed a higher cloning efficiency, proliferated more rapidly in response to cytokine stimulation and generated more progeny than the CD34 + CD38 Ϫ cells from BM counterparts. 8 In part, the higher proliferative potential of primitive cells from UCB may be ascribed to their ability to leave the dormant state more rapidly than their BM counterparts. 14 In vivo functional differences among human stem cells from s...

supporting

confidence: 70%

Similar myeloid recovery despite superior overall engraftment in NOD/SCID mice after transplantation of human CD34+ cells from umbilical cord blood as compared to adult sources

Noort

Wilpshaar

Hertogh

et al. 2001

“…A related transplant, recipient's CMV sero-positive status and higher cell dose were associated with faster T-cell recovery, while this was delayed in the presence of acute GVHD. Other studies have reported similar results; 31,33,57 however, no correlation was found between NC dose and time to immune recovery 33 (Table 6). At 3 months after CBT immunoglobulin levels were normal, while numbers and function of T cells were significantly decreased, 56 in vitro responses to mitogen stimulation were detectable at 3 months after unrelated CBT and became normal at 6 months.…”

supporting

confidence: 72%

Hematopoietic stem cell transplantation using umbilical cord blood progenitors: review of current clinical results

Benito

Díaz

González‐Vicent

et al. 2004

Summary:Umbilical cord blood (CB) has been rapidly established as an alternative source of stem cells to bone marrow for allogeneic-related and unrelated hematopoietic transplantation. To date, almost 70 000 CB units are available for transplantation and more than 2000 CB transplants (CBT) have been performed, mostly in children, for the treatment of a variety of malignant and nonmalignant conditions. Considerable experience has been rapidly accumulated in this field and many aspects of CBT have been elucidated, while other questions remain unresolved. A concise review of the clinical results achieved after related and unrelated CBT is presented and discussed.

“…However, there are some reports of delayed immune recovery after CBT, in which transplant procedures involved ATG and mPSL for conditioning and GVHD prophylaxis. 21,22 In the present case, hematopoesis was supported by autologous hematopoietic recovery, and not comparable to previous studies that attained donor-derived complete chimerism. However, dysfunctional immunological reconstitution was observed soon after CBT, concurrently with irradiated autologous hematopoietic recovery.…”

Section: Total 20supporting

confidence: 60%

“…Although several studies have examined T cell recovery after CBT, 4,10,[20][21][22] little is known about immune reconstitution after myeloablative doses of irradiation. We documented the early immune reconstitution after a two loci HLA-mismatched CBT in an adult recipient compared to that seen with bone marrow, avoiding the use of ATG and mPSL in the conditioning and GVHD prophylaxis.…”

Section: Total 20mentioning

confidence: 99%

Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim

Nagayama

Misawa

Tanaka

et al. 2002

Summary:We performed stem cell rescue and allogeneic skin transplantation on a lethally neutron-irradiated nuclear accident victim. HLA-DRB1 mismatched unrelated umbilical cord blood cells (2.08 ؋ 10 7 /kg recipient body weight) were transplanted to an 8-10 Gy equivalent neutron-irradiated patient because of a lack of a suitable bone marrow or peripheral blood donor. Pre-transplant conditioning consisted of anti-thymocyte ␥-globulin alone, and GVHD prophylaxis was a combination of cyclosporine (CYA) and methylprednisolone (mPSL). Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoietin (TPO) were concurrently administered after transplantation. The absolute neutrophil count reached 0.5 ؋ 10 9 /l on day 15, the reticulocyte count rose above 1% on day 23, and the platelet count was over 50 ؋ 10 9 /l on day 27, respectively. Cytogenetic studies of blood and marrow showed donor/recipient mixed chimerism. Rapid autologous hematopoietic recovery was recognized after withdrawal of CYA and mPSL. Repeated pathological examinations of the skin revealed no evidence of acute GVHD. Eighty-two days after the irradiation, skin transplantation was performed to treat radiation burns. Almost 90% of the transplanted skin engrafted. Immunological examination after autologous hematopoietic recovery revealed an almost normal T cell count. However, immune functions were severely impaired. The patient died from infectious complication 210 days after the accident.