Hematopoietic Cell Transplantation (HCT) For Fanconi Anemia (FA): Comparable Outcomes Regardless Of Stem Cell Source

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3706-3706
Author(s):  
Margaret L. MacMillan ◽  
Todd E. Defor ◽  
John E. Wagner
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Genetic Diagnosis ◽  
Young Patients ◽  
Organ Function ◽  
Hematopoietic Stem ◽  
Vitro Fertilization ◽  
Sibling Donor ◽  
Matched Sibling

Abstract Historically, outcomes after alternative donor (AD)-HCT for FA have been strikingly inferior to those observed in recipients of HLA-matched sibling donor (MSD) hematopoietic stem cells (HSC) with excessive rates of graft failure, graft-versus-host-disease (GVHD), regimen related toxicity and infection, resulting in poor survival rates. Between 2006-2013, 44 FA patients with marrow aplasia and good organ function underwent AD-HCT after total body irradiation 300 cGy (single fraction) with thymic shielding, fludarabine (FLU) 140 mg/m2, cyclophosphamide (CY) 40 mg/kg and antithymocyte globulin (ATG). Outcomes were compared to those transplanted with HSC from an HLA matched sibling donor (n=24) after FLU 175 mg/m2, CY 20 mg/kg and ATG conditioning (1999-2013). GVHD preventative measures were identical with all recipients of marrow having the graft T cell depleted by CD34 selection (regardless of donor type) prior to infusion in addition to cyclosporine A and methylprednisolone or mycophenolate mofetil. Recipients of umbilical cord blood had no additional graft processing. Except for higher use of pre-HCT G-CSF in recipients of AD-HCT, patient characteristics were similar between the 2 groups. Probabilities of neutrophil recovery, acute and chronic GVHD were similar between the groups (Table 1). Most notably, probability of survival at 3 years was the same between the two groups (Figure 1). To our knowledge, this is the first demonstration of comparable outcomes after AD-HCT and MSD HCT for FA patients with marrow aplasia. These findings have three important implications: 1) timing for HCT need not be delayed if the patient lacks an HLA matched sibling donor, 2) potentially reduced enthusiasm for in vitro fertilization and preimplantation genetic diagnosis to have a 'savior sibling' and 3) ineligibility of FA young patients with a suitable AD (HLA matched adult volunteer or 5-6/6 matched UCB) and good organ function for high risk trials, including gene modified HSC. Disclosures: Wagner: Novartis: Research Funding.

The Outcomes of Preimplantation Genetic Diagnosis Therapy in Treatment of β Thalassemia - a Retrospective Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3783-3783
Author(s):  
Naveen Qureshi ◽  
Drucilla Foote ◽  
Rebecca Madore ◽  
Mark C. Walters ◽  
Sylvia Titi Singer ◽  
...  
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Therapeutic Option ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Vitro Fertilization ◽  
Blastomere Biopsy ◽  
Sibling Donor

Abstract BACKGROUND: β thalassemia is one of the most common single gene disorders. Hematopoietic stem cell transplantation (HCT) from a human leukocyte antigen (HLA)-identical sibling donor is a curative option that minimizes the risk of graft-versus-host disease, compared to alternative donor HCT. In families that have an affected child, preimplantation genetic diagnosis (PGD) can be utilized to select an unaffected embryo that is HLA-identical. Briefly, this procedure requires in vitro fertilization, oocyte retrieval, fertilization and blastomere biopsy for preimplantation analysis and identification of unaffected HLA-identical embryos. After delivery, umbilical cord blood from the sibling donor is collected for HCT. In our institution, PGD has been pursued as a therapeutic option by families with thalassemia. The estimated cost of this uninsured procedure is $20,000 per cycle. METHODS: Families affected with β thalassemia who attempted PGD were identified and reviewed for indication, attempted cycles, successful pregnancy and transplantation outcome. RESULTS: Eight identified families affected by thalassemia underwent PGD. The diagnosis of their affected children included: 6 cases of β thalassemia major and 2 cases of transfusion dependent E β thalassemia patients. A total of 14 cycles of PGD were attempted, ranging from 1–4 attempts per family. Following successful identification of HLA-identical cells, 2 pregnancies occurred (1 early miscarriage, 1 successful delivery). This pregnancy resulted in the engraftment of a β thalassemia child. CONCLUSION: PGD including selection of HLA-identical sibling embryos is a novel, therapeutic approach for patients with β thalassemia. While this offers the possibility of recruiting a suitable donor for HCT, it is limited by significant financial and emotional burdens that it places on families affected with β thalassemia. Improvements in its efficiency and cost will make this a more viable option for affected families.

Successful Stem Cell Tranplant Following HLA Identical Sibling Selection Using PGD Combined With HLA Typing In a Case Of CD40 Ligand Deficiency

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4514-4514
Author(s):  
Nazia Tabassum ◽  
Celia Gonzalez ◽  
Karen Anthony ◽  
Jignesh Dalal
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Genetic Diagnosis ◽  
Cd40 Ligand ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Sibling Donor ◽  
Matched Sibling

Pre-Implantation genetic diagnosis and pre implantation Human Leukocyte Antigen (HLA) typing has been successfully used to conceive unaffected HLA identical siblings to provide stem cells for Hematopoietic Stem Cell Transplant (HSCT) (Goussetis, Evgenios, et al. Biology of Blood and Marrow Transplantation 16.3 (2010): 344-349). This technique has been effective in treatment of disease such as Leukemia, Diamond-Blackfan anemia, Thallasemia etc. With improvement of molecular techniques it has been possible to do gene testing from a single cell. We report first case of X-linked Hyper CD40 ligand deficiency where preimplantation genetic diagnosis (PGD) and pre implantation HLA typing were used to achieve successful HSCT from the resulting HLA identical sibling donor. We used dual hematopoietic stem cell sources from cord blood and bone from the nine month old sibling. Currently, patient is 34 months post transplantation doing well with full immunologic reconstitution. Patient was a 14 month old male who presented with a 2 month history of intermittent fever & poor oral intake. He was drooling excessively and tired on appearance. He had also developed mouth sores and later worsening stridor. Chest x-ray revealed right-sided patchy infiltrates. A laryngoscopy was performed that showed supraglottic stenosis. He was transferred to the PICU where he was intubated, ventilated and treated with 10 days of Meropenem. He was later extubated when it was confirmed that there was healing of the supraglottic area. Patient had Leukopenia and received GCSF. Labs also showed decreased level of IgG, IgA and elevated IgM with low titers to tetanus, H flu and diphtheria vaccines. HIV test was negative. His CD40 ligand test revealed deletion of Exon 2 (Figure 1) confirming the diagnosis. Patient's mother was also confirmed to be a carrier for the mutation. He was started on IVIG supplementation and later subcutaneous Ig. When the patient was diagnosed, he had no siblings but his mother was in the first trimester of a pregnancy. HLA typing was done utilizing chorionic villus sampling. Unfortunately, the fetus was found not to be a match and efforts were directed at finding an unrelated donor through multiple donor drives. A well matched unrelated donor was not available after multiple attempts and donor drives for two years. Cord blood transplant and mismatched unrelated donor transplant were considered. Transplants utilizing mismatched unrelated donors for CD40 ligand deficiency are rare and are associated with an increased risk of complications as well as lower overall survival rate. Due to these factors, the parents declined these options for transplant. Parents then decided to pursue PGD with Preimplantation HLA Testing. After PGD and combined HLA testing an unaffected embryo that was a HLA match to the patient was selected after multiple attempts (Figure 2). The mother underwent IVF with the selected embryo and delivered a male sibling. The genetic testing for CD40 ligand deficiency and HLA typing was repeated on the proposed donor baby after birth. The repeat tests confirmed that the proposed donor baby was unaffected and a 10 of 10 HLA match for the patient. The patient was subjected to a conditioning regimen consisting of Busulfan, Cytoxan and GVH prophylaxis with Methotrexate and Tacrolimus. Following the regimen, the patient was infused with stem cell dose consisting of fresh bone marrow (1.86x108 TNC/Kg) harvested from the matched sibling donor and cryopreserved cord blood (0.29x108 TNC/Kg) obtained during the sibling donor's birth. The patient was found to be well engrafted (98% on day 18, 100% at 9 months) post transplant. The CD40L test showed 60% CD40L on T cells after stimulation with ICOS (inducible co-stimulator) increased from 0% pre-transplant. Most patients with hyper CD40 ligand deficiency inherit the causative gene mutation from one of their parents. The average family size in the US is 3.14 (Daphne Lofquist, et al. Households and Families: 2010 Census Briefs).This results in a low probability of finding a sibling donor that is both unaffected and a HLA match. Undergoing multiple pregnancies with low probabilities of conceiving an unaffected HLA matched sibling is stressful, time consuming and ineffective. PGD combined with HLA typing provides an effective way of choosing an embryo that result in a matched HLA donor sibling and subsequent successful stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

Similar Outcomes of Allogeneic Hematopoietic Cell Transplantation from Matched Sibling Donor and Haploidentical Donor for Refractory/Relapsed Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5511-5511
Author(s):  
Dai-Hong Liu ◽  
Li Yu ◽  
Wenrong Huang ◽  
Liping Dou ◽  
Honghua Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Stem Cell ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Sibling Donor ◽  
Matched Sibling

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only effective, even curative treatment for refractory/relapsed AML patients. Unmanipulated haploidentical HCT (haplo-HCT) resulted in encouraging outcomes for treatment of hematologic malignancies and become an alternative option in case of lacking HLA matched sibling donor (MSD). Unmanipulated haplo-HCT from G-CSF mobilized bone marrow and peripheral blood stem cell (PBSC) has shown similar results as that from MSD-HCT in leukemia. Here, we report the results of a cohort study on the efficacy and toxicity of haplo-PBSCT compared with MSD-PBSCT for treatment of refractory/relapsed AML. PATIENTS AND METHODS Among 419 newly diagnosed AML patients, 69 patients relapsed during CR1 and were planned to receive allo-HCT after re-induction. The order of preference of donors was MSD, matched unrelated (HLA 10/10 or 9/10 loci matched), or haploidentical donor. Thirty patients received haplo-PBSCT and 13 patients MSD-HCT (July, 2007 ~ June, 2014) at our unit. There was no difference of the characteristics of demography, disease or transplantation between these two groups (Table 1). High-resolution DNA techniques were used to evaluate the HLA-A, B, DRB1, DQB1, and C loci. Donors were treated with rhG-CSF (5 mg.kg-1.day-1) for consecutive days. The PBSCs were collected on day 5 - 6 and infused on the day of collection. The conditioning regimen consisted of Bu (9.6 mg.kg-1, intravenously, days -10 ~ -8), Carmustine, (250 mg.m-2, day -5), cytarabine (8 g.m-2, days -7 ~ -6), CY (120 mg kg-1, days -4 ~ -3), and ATG (rabbit; 10 mg.kg-1, days -5 ~ -2). MSD-HCT patients had the same conditioning regimen without ATG. All transplant recipients received cyclosporine A, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. The endpoint of the last follow-up for all surviving patients was June 30, 2015. RESULTS Sustained myeloid engraftment with full donor chimerism was achieved in both groups (100%) at a median of 16 (10 - 26) days. Twenty-six patients (86.7%) in haplo-PBSCT group and all patients in MSD-PBSCT group achieved platelet recovery. There was no difference of the cumulative incidence of acute GVHD grade 2-4 (Fig. 1), chronic GVHD (20% vs 33.3%, P=0.581), transplantation-related mortality (TRM) (16.7% vs 0%, P = 0.121), relapse (33.3% vs 38.5%, P = 0.578, Fig 2) between haplo-PBSCT and MSD-PBSCT group. Donor age of 41yr and older was an independent risk factor for inferior leukemia-free-survival (27.8% vs 37.2%, P = 0.004). CONCLUSION In this cohort study, haplo-PBSCT showed similar outcomes in patients with refractory/relapsed AML compared with MSD-PBSCT. It suggested the feasibility of G-CSF-primed PBSC as a graft source in unmanipulated haplo-HCT under myeloablative conditioning, which was effective and tolerable for treatment of poor risk leukemia. Table 1. Characteristics of patients and donors Haploidentical donor Matched sibling donor P value Cases % Cases % Gender, n (%) Receipt Male 22 73.3 8 61.5 0.485 Donor Male 22 73.3 7 53.8 0.292 Age,y, median(range) Patient ≤40 y, n (%) 21 70 6 46.2 0.178 Donor ≤41 y, n (%) 13 43.3 5 38.5 1.000 AML, n (%) 1.000 CR2 5 16.7 2 15.4 NR/beyond CR2 25 83.3 11 84.6 Time to transp 0.51 ≥7m 14 46.7 8 61.5 Conditioning Regimen, n (%) 0.675 BuCy 22 73.2 9 69.2 TBIcy 4 13.3 1 7.7 FB 4 13.3 3 23.1 CD34+ in graft (106/kg) 0.499 ≥4.77 17 56.7 5 41.7 Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

scholarly journals Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1397-1400 ◽  
Author(s):  
Hubert Schrezenmeier ◽  
Jakob R. Passweg ◽  
Judith C. W. Marsh ◽  
Andrea Bacigalupo ◽  
Christopher N. Bredeson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Young Patients ◽  
Graft Versus Host ◽  
Sibling Donor ◽  
Peripheral Blood Progenitor Cells ◽  
Matched Sibling ◽  
Overall Mortality

AbstractWe analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic graft-versus-host disease (GVHD) were similar after PBPC and BM transplantations regardless of age at transplantation. In patients older than 20 years, chronic GVHD and overall mortality rates were similar after PBPC and BM transplantations. In patients younger than 20 years, rates of chronic GVHD (relative risk [RR] 2.82; P = .002) and overall mortality (RR 2.04; P = .024) were higher after transplantation of PBPCs than after transplantation of BM. In younger patients, the 5-year probabilities of overall survival were 73% and 85% after PBPC and BM transplantations, respectively. Corresponding probabilities for older patients were 52% and 64%. These data indicate that BM grafts are preferred to PBPC grafts in young patients undergoing HLA-matched sibling donor transplantation for SAA.

scholarly journals Similar Incidence of Severe Acute Gvhd and Less Extensive Chronic Gvhd in PBSCT from Unmanipulated Haploidentical Donor Compared with That from Matched Sibling Donor for Patients with Hematologic Malignancies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1964-1964
Author(s):  
Honghua Li ◽  
Wenrong Huang ◽  
Chunji Gao ◽  
Liping Dou ◽  
Fei Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem ◽  
Sibling Donor ◽  
Matched Sibling ◽  
Similar Incidence

Abstract Unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HCT) resulted in encouraging outcomes for treatment of hematologic malignancies and become an alternative option in case of lacking HLA matched sibling donor (MSD). Transplantation with G-CSF mobilized peripheral blood stem cell (PBSCT) has been a stable transplant setting with MSD. Unmanipulated haploidentical donor (haplo-PBSCT) has been applied in patients with hematologic malignancies. However, the characteristics of graft-versus-host disease (GVHD) in unmanipulated haplo-PBSCT are not clear. Here, we report the results of a cohort study on the clinical features of acute and chronic GVHD in haplo-PBSCT compared with PBSCT from MSD in patients with hematologic malignancies. PATIENTS AND METHODS Between July, 2007 and June, 2014, 94 patients with hematologic malignancies received haplo-PBSCT and 100 patients received PBSCT from MSD consecutively at our unit (Table 1). The PBSCs were collected on day 5 and 6 after 4 days of rhG-CSF (5 mg.kg¨C1 °¤day¨C1), then were infused on the day of collection. The conditioning regimen consisted of Bu (9.6 mg.kg-1, iv, days -10~-8), Carmustine, (250 mg.m-2, day -5), cytarabine (8 g.m-2, days -7~-6), CY (120mg kg-1, days -4~-3). Antithymoglobulin (ATG, rabbit; 10 mg.kg-1, days -5~-2) was used for haplo-PBSCT. All recipients received cyclosporine A, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. The endpoint of the last follow-up for all surviving patients was July 15, 2015. RESULTS Among the patients with acute GVHD, there was no difference of the rate of the involved organs between these two groups (skin: 67.4% vs 68.0%, p=1.000; liver: 15.2% vs 20.0%, p=0.742; gut: 33.3% vs 32%, p=1.000). Haplo-PBSCT was associated with higher incidence of acute GVHD grade 2-4 (HR: 3.04, 95% CI: 1.55-5.98, p=0.001) and lower incidence of extensive chronic GVHD (HR: 0.49, 95% CI: 0.24-0.99, p=0.047) compared with MSD PBSCT. There was no difference of the incidence of acute GVHD grade 3-4 between these two groups (haplo-PBSCT, 9.6% vs MSD PBSCT 8.9%, p=1.000). According to NIH criteria, the incidence of severe chronic GVHD was lower in haploidentical group (13.6%) compared with MSD group (40.5%, p=0.041). There was no difference of those for mild and moderate chronic GVHD (mild: 27.3% vs 13.5%, p=0.189; moderate: 59.1% vs 45.9%, p=0.422). CONCLUSION In this cohort study, haplo-PBSCT was associated with similar incidence of severe acute GVHD, lower extensive chronic GVHD and lower severe chronic GVHD compared with MSD-PBSCT. It suggested the potential advantage of ATG in improvement of long-term quality of life of the transplant recipients. Table 1. Characteristics of patients and donors Haploidentical donor, n = 94 Matched sibling donor, n = 100 P value Gender, n (%) Receipt, male 73 (77.7) 64 (64.0) 0.041 Donor, male 63 (67.0) 60 (60.0) 0.371 Age Patient, y, median 27 38 0.055 Donor, y, median 38 39 0.364 Hematologic malignances, n (%) Acute leukemia 72 (76.6) 61 (61.0) MDS 3 (3.2) 21 (21.0) 0.000 CML 5 (5.3) 10 (10.0) Lymphoma 14 (14.9) 8 (8.0) Status of disease, n (%) 0.000 CR1 42 (44.7) 76 (76) CR2 14 (14.9) 5 (5) NR/beyond CR2 38 (40.4) 19 (19) Time to transplant (d) 361 299 0.946 Conditioning Regimen, n (%) 0.354 BuCy 60 (63.8) 66 (66.0) TBIcy 28 (29.8) 23 (23.0) FB 6 (6.4) 11 (11.0) CD34+ in graft (106/kg) 5.86 4.77 0.057 ≥4.60 51 (54.3) 41 (41.0) 0.084 Disclosures No relevant conflicts of interest to declare.

HLA-Identical Embryos Selected after in Vitro Fertilization and Pre-Implantation Genetic Diagnosis Combined with HLA Typing: A Promising Option for Successful Allogeneic Hematopoietic Stem Cell Transplantation for Children with Genetic or Malignant Disorders Who Lack an HLA-Matched Related or Unrelated Donor

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2536-2536
Author(s):  
Eugene Goussetis ◽  
Panagiotis Tsirigotis ◽  
Ioulia Peristeri ◽  
Vassiliki Kitra ◽  
Georgia Avgerinou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
In Vitro Fertilization ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Genetic Diagnosis ◽  
Hla Typing ◽  
Hematopoietic Stem ◽  
Vitro Fertilization

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for many children with various genetic or malignant diseases. However not all children in need for HSCT have a suitable donor available. For such cases in vitro fertilization (IVF) with pre-implantation genetic diagnosis (PGD) combined with human leukocyte antigen (HLA) tissue typing has been used to select an IVF healthy and HLA-matched embryo in order to give birth to a child who may serve as a stem cell donor. We report our experience with five children transplanted from HLA-matched siblings selected after IVF and PGD in our center. Methods and Patients: The clinical protocol was approved by the center’s Institutional Research and Ethics Committee. Written informed consent was obtained from parents. Hormonal stimulation for IVF, culture techniques, PGD and HLA-typing were performed according to standard protocols. Detection of the genetic disease mutation was performed by using mini-sequencing. Embryos genotyping was performed by using multiplex polymerase chain reaction (PCR) analysis of informative polymorphic short tandem repeat (STR) markers. Healthy and HLA-identical embryos were transferred 6 days after fertilization to the uterus of the respective mothers. Confirmatory genetic testing and HLA-typing were performed during the first trimester of pregnancy by using chorionic villus sampling. Patient’s characteristics are shown in Table 1. None of our patients had an available matched sibling donor. All patients underwent myeloablative conditioning consisting of busulfan, cyclophosphamide and antithymocytic globulin. GVHD prophylaxis consisted of CyA plus Methotrexate. Stem cell graft consisted of bone marrow plus cord blood in 4 out of 5 patients, while one patient received bone marrow only. Results: All couples underwent a single cycle of IVF resulting into the generation of 78 embryos. Fourteen embryos were healthy and HLA-identical with their sibling and 10 of them were transferred to the uterus of the respective mother giving birth to a total of 6 healthy children. Results of IVF, PGD and HLA-typing are shown in more detail in Table 2. The median age of the donor at the time of HSCT was 16 months. The median total nucleated cell (TNC) concentration of cord blood grafts was 2.3x107/kg, while the median CD34+ cell was 0.47x105/kg. The median TNC and CD34 cell concentration of bone marrow grafts was 1,97x108/kg and 5,09x106/kg respectively. All patients achieved sustained engraftment of donor cells. Mild acute GVHD of the skin was observed in one out of 5 patients. As of today, with a median follow up period of 4 years, all patients are alive with complete donor chimerism, without chronic GVHD and free of disease. Conclusions: IVF and PGD/HLA typing methodology should be considered and discussed with parents in cases where no HLA-matched donor is available. The procedure can be applied only in cases requiring non-urgent HSCT, and in parents of reproductive age. Table 1:Patient’s characteristicsPatientSexAge (years)DiseasePrevious treatmentsDate of transplant1Male4,5Chronic granulomatous diseaseInterferon-gamma, antibiotics2/10/20072Male4Chronic granulomatous diseaseantibiotics1/7/20083Male11Chronic myeloid leukemiaHydroxyurea, imatinib21/7/20094Male4Thalassemia majorRBC transfusions4/5/20105Female4,5Diamond-Blackfan anemiaCorticosteroids, RBC transfusions30/4/2013 Table 2: Results of IVF, PGD and HLA-typing Patients IVF (cycles) Number of embryos after IVF Number of healthy and HLA-identical embryos Number of healthy and HLA-identical transferred embryos Number of healthy and HLA-identical borned children 1 1 37 6 2 1 2 1 11 2 2 1 3 1 10 2 2 1 4 1 10 1 1 1 5 1 10 3 3 2 Disclosures No relevant conflicts of interest to declare.

scholarly journals Occurrence and Impact of Minor Histocompatibility Antigens' Disparities on Outcomes of Hematopoietic Stem Cell Transplantation from HLA-Matched Sibling Donors

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Monika Dzierzak-Mietla ◽  
M. Markiewicz ◽  
Urszula Siekiera ◽  
Sylwia Mizia ◽  
Anna Koclega ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Histocompatibility Antigens ◽  
Hematopoietic Stem ◽  
Minor Histocompatibility Antigens ◽  
Negative Effect ◽  
Matched Sibling

We have examined the alleles of eleven minor histocompatibility antigens (MiHAs) and investigated the occurrence of immunogenic MiHA disparities in 62 recipients of allogeneic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning performed between 2000 and 2008 and in their HLA-matched sibling donors. Immunogenic MiHA mismatches were detected in 42 donor-recipient pairs: in 29% MiHA was mismatched in HVG direction, in another 29% in GVH direction; bidirectional MiHA disparity was detected in 10% and no MiHA mismatches in 32%. Patients with GVH-directed HY mismatches had lower both overall survival and disease-free survival at 3 years than patients with compatible HY; also higher incidence of both severe acute GvHD and extensive chronic GVHD was observed in patients with GVH-directed HY mismatch. On contrary, GVH-directed mismatches of autosomally encoded MiHAs had no negative effect on overall survival. Results of our study help to understand why posttransplant courses of allo-HCT from siblings may vary despite the complete high-resolution HLA matching of a donor and a recipient.

The experience of holding the cycles of assisted reproductive technology with defrost, a biopsy, genetic study and refreezing of embryos in patients with multiple unsuccessful implantations

2016 ◽  
pp. 166-170
Author(s):  
Y.V. Masliy ◽  
◽  
I.O. Sudoma ◽  
P.S. Mazur ◽  
D.A. Mykytenko ◽  
...  
Keyword(s):  
Chromosomal Rearrangements ◽  
Genetic Diagnosis ◽  
Morphological Characteristics ◽  
Implantation Rate ◽  
Ovarian Response ◽  
Reproductive Technologies ◽  
Comparative Genome Hybridization ◽  
Comparative Genome ◽  
Vitro Fertilization

The objective: to study the possibility of using frozen blastocysts for biopsy and genetic testing and performance measurement transfer euploeded 5–7-day-old embryos after thawing, biopsies, refreezing and thawing in patients with unsuccessful implantation. Patients and methods. The object of the study was the group of patients with repeated failure of implantation (4) in programs of auxiliary reproductive technologies (ART), subject to transfer to the uterus in total (i.e. in all the programs) for at least 6 good quality embryos based on morphological characteristics). All women had sufficient ovarian reserve. The patient was treated for infertility within the ART programs of the clinic of reproductive medicine "Nadiya" in the period from 2006 to 2016. The sample included couples who were not carriers of chromosomal rearrangements, without anomalies of the uterus (congenital and acquired: a doubling of the uterus, one-horned uterus, intrauterine membrane, synechia, submucous myoma of the uterus). All women had a positive ovarian response to controlled stimulation with gonadotropins (at least 7 oocytes) and a sufficient number of cryopreserved embryos. The first group (G1) included 64 women who trophectodermal a biopsy was performed on fresh blastocysts (in a loop controlled ovarian hyperstimulation). The second group (G2) were included 31 women who underwent thawing previously cryopreserved blastocysts trophectodermal re-biopsy and vitrification of blastocysts. Results. It was found that the performance of transfers euploid embryos that were vitrified, bioptrone and revitriphted, a little lower than those that were bioptrone fresh and vitrified only once. At the same time computationa genetic diagnosis previously vitrified blastocysts using comparative genome hybridization in patients with recurrent failed implantation allows to obtain a reasonable pregnancy rate (58%), implantation rate (33.3 %) and the birth of living children (45.1 %). Conclusion. Reprising biopropane embryos does not cause significant destructive impact and allows you to achieve pregnancy and birth of the alive child. Key words: in vitro fertilization, reusable unsuccessful implantation, a method of comparative genome hybridization, refreezing.

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