PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Transplantation, Haploidentical”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1996

Specific depletion of alloreactivity against haplotype mismatched related individuals by a recombinant immunotoxin: a new approach to graft-versus-host disease prophylaxis in haploidentical bone marrow transplantation.

Haploidentical bone marrow transplantation (BMT) is associated with a high risk of severe graft-versus-host disease (GVHD). While pan-T cell depletion of the graft is the most effective means of preventing severe GVHD, it is associated with delayed recovery of T cell function leading to fatal infections. We used two related Pseudomonas exotoxin-based immunotoxins, anti-Tac(Fv)-PE38 and anti-Tac(Fv)-PE38KDEL, that both target the IL-2 receptor on activated T cells, to specifically deplete alloreactive lymphocytes against haploidentical stimulators. The functional capacity of the remaining lymphocytes was tested in proliferative assays against the original haploidentical stimulator and pooled cells from other mismatched donors (third party). We varied the recombinant toxin concentration and schedule to determine the optimum conditions for selective depletion. In 10 experiments, the mean residual reactivity after depletion was 7.6 +/- 1.4% against the haploidentical stimulator and 64.2 +/- 5% against the third party, expressed as a percentage of the undepleted response to the same stimulators. Depletion was shown to be specific for mixed lymphocyte culture (MLC)-activated lymphocytes. The immunotoxin did not affect CFU-GM growth of normal BM cells. This selective depletion of haploidentical alloreactivity could be used to prevent GVHD while conserving immune recovery following haploidentical BMT.

ADP Ribose Transferases↗
PubMed2004

Megadose CD34+ hemopoietic stem cell transplantation for patients with high risk acute myeloid leukemia who have no HLA matched donor--a pilot study of a full haplotype mismatch transplantation.

BACKGROUND: Haploidentical transplantation has become a popular modality of treatment for acute myeloid leukemia (AML) patients lacking donors with matching HLA. We attempted to assess the success rate and ramifications of full haplotype mismatch transplantation. METHODS: Four patients received stem cell transplantation from their full haplotype mismatched family donors. The conditioning regimen included total-body irradiation, intravenous busulfan, antithymocyte globulin, and fludarabine. Megadose CD34+ stem cell transplants were performed, in a dosage range between 10.9 x 10(6)/kg and 20.6 x10(6)/kg. Neither GvHD prophylaxis nor post-transplant G-CSF were administered. We monitored patients' bone marrow cellularity and peripheral blood chimerism using real-time PCR. RESULTS: All patients evidenced stable engraftment. The most frequent side effect was severe mucositis, but all patients recovered successfully, without early death. No patients exhibited acute GvHD. Two refractory patients relapsed soon after transplantation. The other 2 patients have remained in good clinical condition, with a follow-up duration of 1-4 months. CONCLUSION: Using a newly-developed conditioning regimen, we were able to circumvent GvHD and graft failure, which are the main limitations associated with full haplotype mismatch transplantation. According to our analysis of the relevant literature, it appears that this is the first report of such a conditioning regimen.

Adolescent↗
PubMed2002

G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia.

Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versus-graft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 microg/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34(+) and CFU-GM cells, reduced total lymphocytes and reversed the CD4(+)/CD8(+) ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60 +/- 7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.

Adolescent↗
PubMedDate not supplied

Steroid-refractory cutaneous graft-versus-host disease after transplantation of haploidentical parental CD34+ cells in children with Down's syndrome and recurrent acute leukemia.

PURPOSE: This study evaluated the feasibility of performing haploidentical CD34+ selected transplants for children with Down's syndrome (DS) and recurrent leukemia. PATIENTS AND METHODS: Within a cohort of 15 children, two patients had DS. Transplantation of CD34+ cells from haploidentical parents was performed after the children were conditioned with fractionated total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and a short course of methotrexate. RESULTS: The preparative regimen was well tolerated, and engraftment of polymorphonuclear cells and platelets took place promptly (by day 20) in both patients with DS. However, both patients with DS experienced severe grade IV GVHD that was limited to the skin and was refractory to salvage with high-dose methylprednisolone therapy. In one patient, GVHD responded to second-line salvage therapy with ATG, but the patient died on day 234 from leukemic relapse. The second patient had GVHD that did not respond to ATG and died of multisystem organ failure and refractory GVHD on day 44. Two of two DS patients had steroid refractory severe acute GVHD of the skin, while only one of 11 evaluated and identically treated non-DS patients had severe GVHD (p < 0.05). CONCLUSION: These observations in patients who underwent mismatched bone marrow transplantation suggests that patients with DS have an increased risk of severe acute GVHD of the skin in this context.

Antigens, CD34↗
PubMed2005

Successful transplantation of haploidentically mismatched peripheral blood stem cells using CD133+-purified stem cells.

OBJECTIVE: For recipients of haploidentically mismatched stem cell allografts, T-cell depletion is mandatory to prevent lethal graft-vs-host disease (GVHD). Prevention of GVHD can be accomplished by negative selection of T cells or positive selection of stem cells. Recently, a new method for positive selection of stem cells was introduced using monoclonal antibodies against CD133 antigen. We report five cases of successful application of immunomagnetic separation of CD133+ stem cells for haploidentically mismatched allogeneic stem cell transplantation. METHODS: Five patients with high-risk hematological malignancies, ages 7 to 63 years old (median, 17 years), underwent peripheral blood stem cell transplantation from haploidentically mismatched related donors. Conditioning protocol was tailored according to patient clinical situation and included combination of treosulfan/fludarabine/thiotepa/melphalan/Mabcampath. Two patients did not get thiotepa. One of them received a protocol that included infusion of 4.4 x 10(7) blood mononuclear cells from the donor (day -9), followed by a combination of fludarabine/cyclophosphamide/busulfex/MabCampath. Separation of CD133+ stem cells was done using CliniMACS with Miltenyi's CD133 reagent. RESULTS: The procedure was well tolerated by all patients. Early 3-lineage engraftment was documented and none exhibited immune-mediated rejection. Time to recovery of absolute neutrophils count above 0.5 x 10(9)/L and 1.0 x 10(9)/L was 10 to 15 days (median, 14) and 11 to 29 days (median, 15), respectively. Time for platelet recovery to values greater than 20 x 10(9)/L and greater than 50 x 10(9)/L ranged from 12 to 25 days (median, 13.5), and from 14 to 34 days (median, 16), respectively. Transplant-related mortality did not occur in any of the patients. CONCLUSION: Our successful pilot trial suggests that positive selection of CD133+ stem cells may be a useful method for safe transplantation with haploidentically mismatched stem cell allografts while avoiding lethal acute and chronic GVHD. Future studies will be required to assess the clinical benefits of stem cell purification with CD133+ in comparison with CD34+ stem cells.

AC133 Antigen↗
PubMed2005

Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation.

Aspergillus and cytomegalovirus are major causes of morbidity/mortality after haploidentical hematopoietic transplantation. The high degree of mismatching makes cell immunotherapy impossible as it would result in lethal graft-versus-host disease (GvHD). We generated large numbers of donor T-cell clones specific for Aspergillus or cytomegalovirus antigens. We identified clones potentially responsible for causing GvHD by screening them for cross-reactivity against recipient mononuclear cells. Non-recipient reactive, pathogen-specific clones were infused soon after transplantation. They were CD4+ and produced high levels of interferon-gamma and low levels of interleukin-10. In 46 control transplant recipients who did not receive adoptive therapy, spontaneous pathogen-specific T cells occurred in low frequency 9 to 12 months after transplantation and displayed a non-protective low interferon-gamma/high interleukin-10 production phenotype. In the 35 recipients who received adoptive therapy, one single infusion of donor alloantigen-deleted, pathogen-specific clones in the dose range of 10(5) to 10(6) cells/kg body weight did not cause GvHD and induced high-frequency T-cell responses to pathogens, which exhibited a protective high interferon-gamma/low interleukin-10 production phenotype within 3 weeks of infusion. Frequencies of pathogen-specific T cells remained stable over time, and were associated with control of Aspergillus and cytomegalovirus antigenemia and infectious mortality. This study opens new perspectives for reducing infectious mortality after haploidentical transplantations.

Adolescent↗
PubMed1993

Prevention and induction of occlusive coronary vascular disease in autoimmune (W/B)F1 mice by haploidentical bone marrow transplantation: possible role for anticardiolipin autoantibodies.

Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, thrombocytopenia, lupus nephritis, and coronary vascular disease with myocardial infarction (CVD). To determine whether this murine lupus-associated CVD could be transferred to otherwise autoimmune-resistant (C57BL/6 x C3H/He)F1 (B6C3F1) mice via W/BF1 T-cell-depleted marrow (TCDM) transplants, or conversely whether the CVD of W/BF1 mice could be prevented by the reciprocal transplant, reciprocal haploidentical transplants of TCDM were performed. CVD developed only in mice with systemic autoimmunity. Mice that developed lupus had glomerulonephritis and thrombocytopenia and also had elevated titres of autoantibodies to double-strand DNA, cardiolipin, and platelets and elevated levels of circulating immune complexes. Of control W/BF1 mice, 80% developed lupus, and of these, 81% developed CVD with a mean grade of 2.5 +/- 0.8. Engraftment of W/BF1 mice with B6C3F1 marrow protected 90% of the recipients from the development of lupus, and none developed CVD. Engraftment of B6C3F1 mice with W/BF1 marrow induced lupus in 60% of the recipients, and of those, 33% developed CVD with a mean grade of 1.3 +/- 0.3. The B6C3F1 recipients of W/BF1 marrow which developed CVD had significantly higher titres of autoantibodies to cardiolipin (aCL; P < .01). These findings show that genetic abnormalities present in the W/BF1 hematopoietic stem cells contribute to autoantibody development, including aCL, and suggest that thrombogenic mechanisms induced by aCL may contribute to the development of CVD in this form of murine lupus erythematosus.

Animals↗
PubMedDate not supplied

Canadian multicenter pilot trial of haploidentical donor transplantation.

BACKGROUND: Canadian multicenter pilot study of haploidentical donor. AIMS: To assess (1) ability to collect suitable graft (CD34+ > or = 5 x 10(6)/kg and CD3 < 1 x 10(5)/kg recipient body weight), (2) toxicity, (3) survival to day +100. ELIGIBILITY: All hematological malignancies and ages; accrual to end after 20 transplants of patients with AML in remission and age less than 55 years. METHODS: Preparation: Modified Perugia regimen, chemotherapy alone; melphalan 140 mg/m2 day -9, thiotepa 10 mg/kg day -7, fludarabine 40 mg/m2 days -7 to -3, and ATG (Thymoglobulin, Sangstat) days -6 to -2 (total 10.5 mg/kg). Infection prophylaxis: Ganciclovir (GC) 5 mg/kg days 5-20 then x5/week until day +100 then x3/week until 210 (subjects 1-3), foscarnet (FC) 90 mg/kg days 4-21 then short course pre-emptive GC or FC (subjects 4-11); fluconazole; cotrimoxazole. Donors: G-CSF 16 microg/kg daily x5 until second pheresis day. T-cell depletion: CliniMACS (MiltenyiBiotec). RESULTS: Eleven patients with AML have been transplanted from four centers, eight female, three male, median age 34 (range 19-60). Disease status, first CR 1/11, second CR 4/11, third CR1/11, relapse 5/11. Graft CD34+ > or = 5 x 10(6)/kg was achieved in all cases, median 13.72 x 10(6)/kg (Q1, Q3: 8.26, 17.72; min 5.59, max 22.22), and CD3+ was < 1 x 10(5)/kg in all cases, median of 0.49 x 10(4)/kg (Q1, Q3: 0.30, 2.20; min 0.22, max 4.10). Ten of the 11 patients have died, median survival 103.5 days (Q1, Q3: 61.0, 151.0; min 0, max 290.0). Survival to day +100 6/11 (55%). Four patients died of leukemic relapse, six of infection. Of six patients dying of infection, CMV was a definite cause in four. Of four dying with relapse, CMV was significant in one. Engraftment was assessed in 10 patients who survived >0 days. Granulocyte engraftment (> 0.5 x 10(9)/l) was achieved in all patients, median 11.5 days (Q1, Q3: 10, 17; min 8, max 70). Platelet engraftment (> 20 x 10(9)/l) was achieved in 8 of 10 patients, median 15 days (Q1, Q3: 9, 16; min 9, max 97). The two platelet non-engrafters died on days +45 and +61. Toxicity was low, with one toxic death (day 0), and the Bearman organ toxicity gradings were < or = grade 2 in all other patients. There were no instances of graft-vs.-host disease or graft rejection. CONCLUSIONS: The problems of graft-vs.-host disease and graft rejection have been removed as barriers to haploidentical transplantation but the slow immune reconstitution limits its general application. Late referrals contribute to a high relapse rate and have delayed an optimal evaluation of the procedure.

Adult↗
PubMed2004

Transplantation of haploidentically mismatched stem cells for the treatment of malignant diseases.

Hematopoietic stem cell transplantation (HSCT) from HLA haploidentical mismatched donors has recently been developed for patients with high-risk acute leukemia who do not have a matched donor. After a high intensity conditioning regimen the HLA barrier is overcome by infusing a graft containing a megadose of T cell-depleted progenitor cells. Nowadays, for graft processing automated peripheral blood CD34(+) cell immunoselection is time and labor saving and ensures a high CD34(+) cell recovery rate. Besides providing 4.5 log T cell depletion of the graft, it guarantees a 3.5 log B cell depletion, which helps prevent EBV-related lymphoproliferative disorders. Excellent engraftment rates are associated with a very low incidence of graft-versus-host disease and regimen-related mortality even in patients who are over 40 years old. Overall, event-free survival and transplant-related mortality compare favorably with reports from unrelated matched transplants. Donor natural killer cell alloreactivity also plays a role in improving outcome in patients with acute myeloid leukemia. These results show the haploidentical transplant to be a viable, alternative source of stem cells for adults with acute leukemia at high-risk of relapse who do not have matched donors, and encourage extending it to patients with an indication to transplant.

Acute Disease↗
PubMed2002

Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling.

In haploidentical transplantation, the mismatched haplotype of the donor can originate from either of the parents. We refer to such mismatched haplotypes as noninherited maternal antigens (NIMA haplotype) or noninherited paternal antigens (NIPA haplotype). To determine whether exposure to maternal HLA antigens benefits patients undergoing bone marrow transplantation, we analyzed graft failure and graft-versus-host disease (GVHD) after transplantations from parental or haploidentical sibling donors. We studied 269 patients receiving 1 or 2 HLA-A, -B, -DR antigen-mismatched sibling or parental non-T-cell-depleted bone marrow transplants for acute myelogenous leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia between 1985 and 1997 that were reported to the International Bone Marrow Transplant Registry. Included were 121 (45%) NIMA-mismatched and 148 (55%) NIPA-mismatched transplantations. Sixty-three (52%) of the NIMA-mismatched transplants and 69 (47%) of the NIPA-mismatched transplants were from haploidentical sibling donors. Sibling transplantations mismatched for NIMA had similar rates of graft failure but lower rates of acute GVHD (P <.02) than NIPA-mismatched sibling transplantations. In the first 4 months after transplantation, mother-to-child transplantations involved significantly less chronic GVHD than father-to-child transplantations (P <.02). Treatment-related mortality (TRM) was significantly higher after parental transplantations (P =.009 for mother; P =.03 for father) than after haploidentical sibling transplantations mismatched for the NIMA. Non-T-cell-depleted bone marrow transplants donated by haploidentical siblings to recipients mismatched for NIPA and transplants donated by parents caused more acute and chronic GVHD and TRM than transplants donated by haploidentical siblings mismatched for NIMA.

Adolescent↗
PubMedDate not supplied

The role of total body irradiation in the conditioning of patients receiving haploidentical stem cell transplantation.

BACKGROUND: Nearly 40% of patients requiring a hematopoietic stem cell transplant lack a suitable donor. However, virtually all these patients have a potential family donor with whom they share one HLA haplotype. METHODS: We report the rationale for making hematopoietic stem cell transplantation from haploidentical related donors feasible, as well as the method followed to achieve this. Two studies are reported, designed to overcome the problem of rejection and graft-versus-host disease after haploidentical stem cell transplantation. We describe how our total body irradiation-based, highly immuno- and myelosuppressive conditioning regimens were developed and how they have been modified over the years in an attempt to improve the clinical outcome of high-risk acute leukemia patients receiving large numbers of extensively T-cell-depleted hematopoietic stem cell transplantations from full-haplotype mismatched family donors. RESULTS: A high engraftment rate and an extremely low incidence of graft-versus-host disease were obtained. Modifications of the pretransplant schedules allowed the reduction of transplant-related toxicity. CONCLUSIONS: The main obstacles that limited the use of haploidentical stem cell transplantation have been overcome. The procedure is now a reality that should be recommended in high-risk acute leukemia patients who do not have a suitable matched donor.

Acute Disease↗
PubMed1996

Combined in vitro and in vivo T lymphocyte depletion for the control of graft-versus-host disease following haploidentical marrow transplant.

Most patients requiring allogeneic bone marrow transplantation (BMT) lack a human leukocyte antigen genotypically identical sibling and require an alternative donor. This carries an increased risk of graft failure and acute graft-versus-host disease (GVHD). We sought to overcome these problems with transplants by using grafts obtained from the most readily available source: the haploidentical, partially mismatched, related donor. This study of 40 patients used a novel approach combining in vitro and in vivo T cell depletion with T lymphocyte targeted monoclonal antibodies (mAb) and intensified conditioning therapy, including fractionated total body irradiation before etoposide, cytoside arabinoside, cyclophosphamide, and methylprednisolone. Grafts were treated with T10B9.1A-31 mAb, directed against the alpha-beta heterodimer of the T cell receptor, and rabbit complement. In vivo depletion was attempted with an anti-CD5 mAb-Ricin A-chain (H65-RTA) immunotoxin (IT). Study patients were compared with a historical control group of 17 patients not given H65-RTA. Rates of engraftment were not significantly different (93% vs. 100%, P=0.12), although patients receiving IT engrafted more rapidly. The incidence of > grade I GVHD was significantly lower in the study group (36% vs. 100%, P=0.0001), as well as for severe grade III-IV GVHD (19% vs. 92%, P=0.0001). Five-year survival tended to be improved in the study group (40% vs. 18%, P=0.21). Transplant from haploidentical family members is indicated for patients without a matched sibling in whom allogeneic BMT offers the best opportunity to achieve cure.

Adolescent↗
PubMed2004

An open randomized study comparing immunosuppression therapy initiated before or after kidney transplantation in haploidentical living recipients.

BACKGROUND: Acute rejection is the most important risk factor for graft survival. Although many centers start immunosuppressive therapy days before the surgery in living donors, there is no systematic study concerning the possible advantages of this procedure. In this open randomized study, we compared the efficacy and safety of administration of cyclosporine (CSA; Neoral) and azathioprine before renal transplantation with the administration of the same schema after transplantation, in HLA haploidentical grafts. METHODS: Sixty renal transplant recipients of an HLA haploidentical allograft from living donors were randomized in two groups: (A) patients that started immunosuppression 3 d before transplantation (n = 30) and (B) those who started the drug schema on the first day after surgery (n = 30). We analyzed the incidence and severity of acute rejection, graft function and infection during the first 3 months after transplantation. RESULTS: The group of patients who started immunosuppression before had a mean trough level of CSA (299.70 +/- 154.03 ng/mL) in the expected range for an efficacious prevention of acute rejection at the surgery day. Thirteen patients (43.3%) in each group had acute rejection during the follow up (p = 1.00). Two grafts losses (3.3%) occurred, one in each group. Both groups had similar 3-month rejection-free graft survival (56.7 and 56.3%). The incidence of infection was also statistical comparable between groups A and B (56.7 vs. 46.7, p = 0.430). Graft function was similar in patients from both groups. CONCLUSIONS: Pre-transplant administration of immunosuppression did not reduce the incidence or severity of acute rejection episodes during the first 3 months of transplantation. Immunosuppressive drugs administered before engraftment did not increase the incidence of graft dysfunction or infection.

Azathioprine↗
PubMed1995

Dysfunctional cytokine production by host-reactive T-cell clones isolated from a chimeric severe combined immunodeficiency patient transplanted with haploidentical bone marrow.

We have investigated the mechanism of tolerance in a patient with severe combined immunodeficiency (SCID) transplanted with HLA-haploidentical, T cell-depleted bone marrow cells obtained from the mother. At 4 years after transplantation, T cells, natural killer (NK) cells, and a small percentage (2%) of B cells were found to be of donor origin, whereas monocytes and the majority of B cells remained of host origin. In primary mixed lymphocyte cultures (MLC), the engrafted T cells of the donor did not proliferate in response to the host cells, whereas untransplanted donor T cells showed good proliferative responses. However, CD4+ and CD8+ T-cell clones of donor origin with specificity for class II and class I HLA determinants of the host were isolated. CD8+, host-reactive T-cell clones displayed normal cytotoxic activity after stimulation with the host cells, but proliferative responses of CD4+, host-reactive T-cell clones were considerably reduced. In addition, both CD8+ and CD4+, host-reactive T-cell clones produced very low to undetectable levels of interleukin-2 (IL-2), IL-4, IL-5, IL-10, interferon-gamma, and granulocyte-macrophage colony-stimulating factor after specific antigenic activation, which may be responsible for their nonresponsive state in vivo. Expression of the CD3 zeta subunit of the T-cell receptor (TcR) was normal, and after stimulation via CD3, Raf-1 and p42 mitogen activated protein (MAP) kinase were phosphorylated, indicating that this part of the signaling pathway after triggering of the TcR/CD3 complex is present. These results, together with our previous observation that dysfunctional, host-reactive T-cell clones can be isolated in SCID patients transplanted with fetal liver stem cells, demonstrate that lack of clonal deletion of host-reactive T cells is a general phenomenon after HLA-mismatched stem cell transplantation.

Bone Marrow Transplantation↗
PubMed2006

Natural killer cell recognition of missing self and haploidentical hematopoietic transplantation.

Human NK cell function is regulated by clonally distributed inhibitory receptors termed "Killer cell Immunoglobulin-like Receptors" (KIRs) that recognize epitopes ("KIR ligands") shared by HLA-C and HLA-B class I allele groups and every functional NK cell in the repertoire expresses at least one receptor for self HLA-class I molecules. Consequently, when NK cells are confronted with allogeneic targets which do not express the inhibiting class I ligand(s) NK cell alloreactions may occur. Donor versus recipient NK alloreactions occur in full HLA haplotype-mismatched ("haploidentical") hematopoietic transplants that are KIR ligand mismatched in the Graft-versus-Host (GvH) direction. Variable frequencies of functional NK cells in the donor repertoire expressing a KIR for the HLA class I group which is absent in the recipient as their sole inhibitory receptor for self, sense the missing expression of the self class I ligand on allogeneic targets and mediate alloreactions ("missing self" recognition). In clinical trials, donor versus recipient NK alloreactions are highly beneficial as they reduce the risk of leukemia relapse, do not cause GvHD and markedly improve event-free survival.

Animals↗
PubMed2004

In utero hematopoietic stem cell transplantation with haploidentical donor adult bone marrow in a canine model.

OBJECTIVE: Chimerism can be achieved in a canine model of in utero bone marrow transplantation with > or =1 x 10(8) CD34(+) haploidentical donor cells per kilogram without graft-versus-host disease. STUDY DESIGN: In utero bone marrow transplantation was performed by ultrasound-guided intraperitoneal infusion in 30- to 41-day-old canines with CD34(+) selected cells from paternal bone marrow at doses of 1.3 x 10(8) to 2.5 x 10(10) CD34(+) cells/kg. A method for marking control littermates was developed with intraperitoneal ethiodol. Postnatal studies included histologic, fluorescent in situ hybridization canine Y probe, and polymerase chain reaction-based chimerism analyses. RESULTS: Term survival was 86% to 100% for transplantations > or =34 days versus 14% and 43% at 30 and 31 days. Microchimerism (<1%) was demonstrated in tissues from 4 informative litters that included thymus, liver, skin, spleen, and intestine. Neither gestational age nor donor CD34 cell dosage altered the level of engraftment in these experiments. There was no evidence of graft-versus-host disease. CONCLUSION: In utero bone marrow transplantation in a canine model achieves microchimerism with high CD34(+) cell doses.

Animals↗
PubMed1997

Haploidentical family member transplants for patients with chronic myeloid leukaemia: a report of the Chronic Leukaemia Working Party of off European Group for Blood and Marrow Transplantation (EBMT).

Within the registry of the chronic leukaemia working party of the European Group for Blood and Marrow Transplantation, data were available from 103 patients with chronic myeloid leukaemia who were treated by bone marrow transplantation from haploidentical family members. The patients of median age 30 years were transplanted between 1983 and 1994 in 25 European centres. The overall probabilities of survival and leukaemia-free survival (LFS) at 5 years were 32 and 25%, respectively. In univariate analysis, two factors were identified which affected survival and LFS, ie the state of disease at the time of transplant and the degree of HLA disparity. Fifty-nine patients were transplanted in first chronic phase and the probability of survival at 2 years was 47%. Forty-four patients received their transplants for advanced disease and their probability of survival at 2 years was 25% (P = 0.004). Donor bone marrow was HLA-mismatched for 0-1 antigens in 54 patients (group 1) and for 2-3 antigens in 49 patients (group 2). At 2 years, the probabilities of survival for groups 1 and 2 were 46 and 27% (P < 0.02) and the probabilities of LFS were 43 and 24% (P < 0.03), respectively. Multivariate analysis confirmed the prognostic importance of the disease stage and of the HLA disparity. Patients transplanted in first chronic phase from a donor mismatched for 0-1 HLA antigens had a probability of survival of 52% at 2 years compared with 19% for patients transplanted in advanced disease stage from donors mismatched for 2-3 HLA antigens.

Adolescent↗