Haploidentical Stem Research Articles

Haploidentical Allogeneic Haematopoietic Stem Cell Transplantation as Salvage Therapy for Engraftment Failure after Unrelated and Autologous Stem Cell Transplantation: A Case Report and Review of the Literature

Engraftment failure is a rare but life-threatening complication of haematopoietic stem cell transplantation (HSCT) and treatment of this condition is often challenging. This case report describes a patient with acute myeloid leukaemia and engraftment failure after unrelated donor allogeneic stem cell transplantation. Rescue treatment with granulocyte-colony stimulating factor and reinfusion of autologous 'back-up' stem cells failed, but transplantation of haploidentical donor stem cells following a fludarabine and antithymocyte globulin (ATG)-based conditioning regimen resulted in haematological reconstitution and long-term disease-free survival. The use of haploidentical donor stem cell transplantation as salvage therapy after engraftment failure in adult patients has not, to the authors' knowledge, been previously reported. Additionally, a review of the relevant literature is presented. This case report and literature review suggest that reinfusion of cryopreserved 'back-up' haematopoietic stem cells is a safe and effective salvage therapy for engraftment failure after allogeneic HSCT. Haploidentical donor stem cell transplantation after a fludarabine and ATG-based conditioning regimen could provide effective second-line therapy in adult patients.

Unmanipulated Haploidentical Peripheral Blood Stem Cell Transplantation for Precursor T-cell Lymphoblastic Lymphoma Relapsed After Autologous PBSCT

Precursor T-cell lymphoblastic lymphoma (T-LBL) is a clinically aggressive disease, associated with a high subsequent relapse rate. We treated a pediatric patient with T-LBL who relapsed after an autologous peripheral blood stem cell transplantation. Unmanipulated peripheral blood was used as a source for the graft. Hematopoietic engraftment was prompt and the risk of graft-versus-host disease was acceptable. The patient has been in continuous complete remission without chronic graft-versus-host disease for 32 months. Hence, haploidentical peripheral blood stem cell transplantation might be one of the adoptive options for salvage therapy in patients with recurrent or refractory T-LBL, and unmanipulated peripheral blood might be acceptable as a graft.

Clinical efficacy of activated-HLA haploidentical peripheral blood stem cells in treatment of advanced solid tumors

Objective:To evaluate the anti-tumor and side effects of activated-HLA haploidentical peripheral blood tem cells (haplo-PBSCs) in the treatment of advanced refractory solid tumor patients.Methods:Forty-two patients with advanced refractory tumor,who were diagnosed in our hospital from Oct.2004 to Oct.2007,were enrolled in this study (all patients signed informed consent),including 12 with ovarian cancer,9 with renal cancer,8 with lung cancer,8 with breast cancer,2 with colon cancer,2 with gastric cancer,and 1 with melanoma.The donors were healthy direct relatives of the patients;the donors' haplo-PBSCs were mobilized,collected,and activated by rhIL-2 in vitro.The clinical efficacy and side effects of haplo-PBSCs therapy were assessed by CT/PET-CT scanning,RESIST standard,KPS score,and clinical response rates,etc.Results:All 42 patients received one episode of haplo-PBSCs treatment.The progression-free survivals (PFS) were 6 months and the clinical beneficial rate (CR+PR+SD) was 73.8%.The beneficial rate of life quality was 76.2% and the KPS increased by 20 (0-30) points on average after haplo-PBSCs treatment.The patients with KIR unmatched in GVH direction had better outcomes than those with KIR matched or KIR unmatched in HVG direction (P0.05),and the clinical beneficial rate,PFS and total beneficial rate were 94.1% vs 60.0%,(13.4±1.3) vs (8.0±0.9) months,and 89.5% vs 65.2%,respectively (all P0.05).The donor/recipient relation as the mother/child had a better outcome than that as the father/child (P0.05).Patients with renal cancer or ovarian cancer had better outcomes than those with other cancers,with clinical beneficial rates being 90.0% and 81.8%,respectively.Conclusion:Activated haplo-PBSCs therapy can induce non-specific anti-tumor effect,and improve the clinical symptom and life quality of advanced tumor patients.

16-OR: Relevance of inhibitory and activating KIR and HLA ligand on outcomes in reduced intensity haploidentical peripheral blood stem cell transplants

16-OR: Relevance of inhibitory and activating KIR and HLA ligand on outcomes in reduced intensity haploidentical peripheral blood stem cell transplants

127Combination sirolimus and tacrolimus immunoprophylaxis promotes engraftment of haploidentical and alternative donor stem cells with non-myeloablative conditioning in elderly and poor prognosis patients

127Combination sirolimus and tacrolimus immunoprophylaxis promotes engraftment of haploidentical and alternative donor stem cells with non-myeloablative conditioning in elderly and poor prognosis patients

Outcome for children after failed transplant for primary haemophagocytic lymphohistiocytosis.

Primary haemophagocytic lymphohistiocytosis is a rare disorder of childhood, which is usually fatal without allogeneic stem cell transplantation (SCT). For children who lack a matched family or closely matched unrelated donor, SCT using haploidentical parental stem cells has been used, but is associated with an increased risk of graft failure. The most appropriate subsequent management for those children who survive after graft rejection is currently unclear. We report the outcome for three such children. After a period of disease quiescence lasting 4 months to 8 years, disease recurrence and subsequent death occurred in each case. Accordingly, a second SCT is recommended.

In vitro generation of Epstein-Barr virus-specific cytotoxic T cells in patients receiving haplo-identical allogeneic stem cell transplantation.

Use of a partially mismatched related donor (PMRD) is an option for patients who require allogeneic transplantation but do not have a matched sibling or unrelated donor. Epstein-Barr virus (EBV)-induced lymphoma is a major cause of mortality after PMRD transplantation. In this study, we present a clinical grade culture system for donor-derived EBV-specific cytotoxic T cells (CTLs) that do not recognize haplo-identical recipient cells. The EBV-specific CTLs were tested for cytolytic specificity and other functional properties, including ability to transgress into tissues, propensity for apoptosis, degree of clonality, stability of dominant T-cell clones, and Tc and Th phenotypes. The EBV-specific CTLs were routinely expanded to greater than 80 x 10(6) over a period of 5 weeks, which is sufficient for clinical application. A CD8+ phenotype predominated, and the CTLs were highly specific for donor lymphoblastoid cell lines (LCLs) without killing of recipient targets or K562. Vbeta spectratyping showed an oligoclonal population that was stable on prolonged culture. The EBV-specific CTLs were activated (D-related human leukocyte antigen [HLA-DR+], L-selectin+/-) and of memory phenotype (CD45RO+). Expression of the integrin VLA-4 suggested that these CTLs could adhere to endothelium and migrate into tissues. The Bcl-2 message was upregulated, which may protect the CTLs from the apoptosis. The first demonstration of overexpression of bcl-2 in human memory CTLs. In addition, we show that lymphoblastoid cell lines used to generate CTLs are readily genetically modified with recombinant lentivirus, indicating that genetically engineered antigen presentation is feasible.

Transient recovery of endogenous immune function following haploidentical peripheral stem cell transplantation in a patient with severe combined immunodeficiency without evidence of engraftment

Transient recovery of endogenous immune function following haploidentical peripheral stem cell transplantation in a patient with severe combined immunodeficiency without evidence of engraftment

273 Modified T cell MHC restriction following successful haploidentical bone marrow stem cell transplantation in severe combined immunodeficiency disease (SCID)

273 Modified T cell MHC restriction following successful haploidentical bone marrow stem cell transplantation in severe combined immunodeficiency disease (SCID)