Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin.

Biol Blood Marrow Transplant. 2011 Oct;17(10):1460-71

Authors: Sauter C, Abboud M, Jia X, Heller G, Gonzales AM, Lubin M, Hawke R, Perales MA, van den Brink MR, Giralt S, Papanicolaou G, Scaradavou A, Small TN, Barker JN

Abstract
Factors contributing to infection risk after cord blood transplantation (CBT) include the use of anti-thymocyte globulin (ATG), prolonged neutropenia, and failure to transfer immunity. In the present study, we investigated the potential of double-unit CBT without ATG to reduce the risk of infection and evaluated the nature of serious infections in the first year after CBT using this approach. Seventy-two predominantly adult patients underwent CBT for hematologic malignancies; of these, 52 patients received myeloablative conditioning, and 20 received nonmyeloablative conditioning. The peak incidences of bacterial infections (32%), fungal infections (14%), and bacterial/fungal pneumonias (10%) occurred in the first 30 days posttransplantation. Three such infections contributed to early mortality. The peak incidence of viral infections was 31-60 days posttransplantation, affecting 30% of patients. Cytomegalovirus (CMV) was the most common viral infection. CMV infections occurring before day 120 (n = 23) had no relationship with graft-versus-host disease (GVHD), whereas CMV infections occurring after day 120 (n = 5), along with all cases of Epstein-Barr virus viremia (n = 5) and adenoviral enteritis (n = 2), occurred exclusively in the context of GVHD therapy or corticosteroid use for another indication. Viral infections had the highest lethality: 2 were a direct cause of death, and 3 contributed to death. Patients exhibited steady immune recovery, achieving a median CD3(+)4(+) T cell count >200 cells/μL by day 120 post-CBT, and no infection-related deaths occurred after day 120. Our results suggest that double-unit CBT without ATG is associated with prompt T cell recovery, and, unlike in CBT incorporating ATG, infection is rarely a primary cause of death. However, CBT without ATG is associated with a significant risk of GVHD, and serious infections remain a challenge, especially in the setting of GVHD. New strategies are needed to further reduce infectious complications after CBT; these will require earlier neutrophil recovery and more effective prevention of GVHD, ideally without the profound T cell depletion associated with ATG therapy.

PMID: 21310254 [PubMed - indexed for MEDLINE]

Bilateral choroidal detachment after cord blood stem cell transplantation in an adult patient with acute myeloid leukemia.

Int Ophthalmol. 2012 Feb 18;

Authors: Mimura T, Nakashizuka T, Kami J, Kohmura M, Sato S, Dou K, Mori M

Abstract
We report on bilateral choroidal detachment after a cord blood stem cell transplantation procedure. A 52-year-old woman had graft-versus-host disease 49 days after CBSCT for acute myeloid leukemia. She developed bilateral conjunctival chemosis and choroidal detachment 66 days after CBSCT. The annular choroidal detachment gradually increased in both eyes, with no improvement noted over the following month. At 106 days after CBSCT, the patient died from multiple organ failure. Graft-versus-host disease can be associated with bilateral choroidal detachment after CBSCT.

PMID: 22350079 [PubMed - as supplied by publisher]

Successful unrelated umbilical cord blood transplantation in Lesch-Nyhan syndrome.

Metab Brain Dis. 2012 Feb 17;

Authors: Kállay K, Liptai Z, Benyó G, Kassa C, Goda V, Sinkó J, Tóth A, Kriván G

Abstract
Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation, delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation (HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable in LNS as well. Following a myeloablative conditioning regimen (busulphan 3.2 mg/kg/day for 4 days, cyclophosphamide 60 mg/kg/day for 2 days with ATG Thymoglobin 2.5 mg/kg/day for 4 days) an unrelated umbilical cord blood unit was transfused at the age of 2 years. The graft was a 6/6 HLA-matched at HLA-A, B loci by antigen level, and at DRB1 by allelic level typing. Infused total nucleated cell dose was 3.6 × 10e7 per kilogram body weight. Serum HPRT levels reached normal values by the end of the sixth month post transplant. Slow neurodevelopmental improvement seen during the three-year follow-up and the missing self-injuring behavior can be considered as a proof for the presence of enzyme-competent cells behind the blood-brain barrier.

PMID: 22350962 [PubMed - as supplied by publisher]

The challenges of stem cell therapy.

Can J Physiol Pharmacol. 2012 Feb 16;

Authors: Di Nardo P, Singla D, Li RK

Abstract
The actual repairing power of stem cells has yet to be fully realized because of insufficient knowledge about the basic mechanisms regulating their fate and unsuitable protocols to implant them in injured tissues. Novel strategies must be formulated to fully exploit stem cell potential in the clinical setting.

PMID: 22338594 [PubMed - as supplied by publisher]

Open cardiac surgery in the first hours of life using autologous umbilical cord blood.

Eur J Cardiothorac Surg. 2011 Oct;40(4):985-9

Authors: Fedevych O, Chasovskyi K, Vorobiova G, Zhovnir V, Makarenko M, Kurkevych A, Maksymenko A, Yemets I

Abstract
OBJECTIVE: This article describes the first clinical experience of complete repair of complex critical congenital heart diseases (CHDs) in the first hours of life using autologous umbilical cord blood (UCB). Prenatal diagnosis and harvesting of autologous UCB allow to modify perioperative management and to perform corrective surgery in the first hours of a patient's life. This approach can afford avoiding homologous blood transfusion and preventing development of hypoxemia and heart failure due to hemodynamic changes of complex critical CHD.
METHODS: The study group included 14 consecutive prenatally diagnosed patients with critical complex CHD during the period from September 2009 to August 2010. Autologous UCB was harvested in accordance to NetCord-FACT International Standards for Cord Blood Collection and was used during the surgery with cardiopulmonary bypass (CPB). In all cases, complete repair was performed during the first hours of life: arterial switch operation (n=9); arterial switch operation with total anomalous pulmonary venous communication repair (n=1); arterial switch operation with interruption of the aortic arch repair (n=1); Ebstein's repair (n=2); and aortopulmonary window repair with interruption of the aortic arch repair (n=1). All procedures were performed using moderate hypothermia with cold-crystalloid cardioplegia, except one case that required deep hypothermic circulatory arrest.
RESULTS: A mean of 92±16 ml of UCB was harvested. Autologous UCB was used during the surgery in all 14 cases. Mean age of newborns at operation was 4.7±2 h (3-8). No patients required intensive care unit (ICU) admission, interventional procedures, mechanical ventilation, or medications before surgery. Twelve patients underwent bloodless open heart surgery; eight of them completely avoided homologous blood transfusion during the perioperative period. There was one postoperative death in our study (Ebstein's anomaly).
CONCLUSIONS: The use of autologous umbilical cord blood is feasible in neonatal open heart surgery. Complete surgical repair of complex critical CHD can be applied successfully to neonates within the first hours of life.

PMID: 21353580 [PubMed - indexed for MEDLINE]

A comparative analysis of the opinions from European national and international ethics committees regarding the collection, storage and use of umbilical cord blood.

Blood Transfus. 2012 Feb 13;:1-11

Authors: Petrini C

PMID: 22337278 [PubMed - as supplied by publisher]

Painful thyroiditis and subsequent atrophic hypothyroidism after cord blood transfusion.

Thyroid. 2011 Oct;21(10):1157-8

Authors: Makita N, Isojima T, Hiwatari M, Kitanaka S, Ida K, Iiri T

PMID: 21875364 [PubMed - indexed for MEDLINE]

Unrelated cord blood transplantation after myeloablative conditioning regimen in adolescent and young adult patients with hematologic malignancies: a single institute analysis.

Leuk Res. 2012 Feb;36(2):128-31

Authors: Ebihara Y, Takahashi S, Mochizuki S, Kato S, Kawakita T, Ooi J, Yokoyama K, Nagamura F, Tojo A, Asano S, Tsuji K

Abstract
We report the results of unrelated cord blood transplantation (CBT) after myeloablative conditioning regimen in 16 patients with hematologic malignancies from 15 to 20 years old. The median times of myeloid and platelet engraftment were 21 and 38 days, respectively. The cumulative incidences of acute graft-vs-host disease (GVHD) was 62.0%, all of which were grade I or II, and that of extensive-type chronic GVHD was 12.5%. The probabilities of overall and disease-free survival at 3 years were 68.2% and 48.6%, respectively, comparable to adult or childhood cases. Adolescents and young adult patients with hematologic malignancies who have no HLA-matched adult donors could be considered as candidates for CBT.

PMID: 21982638 [PubMed - indexed for MEDLINE]

[Actions of keratinocyte growth factor in leukemic mice allogeneic umbilical cord blood cell transplantation].

Zhonghua Yi Xue Za Zhi. 2011 Nov 1;91(40):2863-7

Authors: Chen GH, Wang Y, Qiao SM, Feng YF, Zhu ZL, Wu DP

Abstract
OBJECTIVE: To explore the actions of keratinocyte growth factor (KGF) in leukemic mice allogeneic umbilical cord blood cell transplantation (UCBT) and elucidate its mechanism.
METHODS: Peripheral blood drawn from the litters of C57BL/6 females was used as umbilical cord blood (UCB) graft. BALB/c mice were randomly divided into 7 groups (n = 12 each). The grouping was as follows. Control group 1, inoculated with leukemia. Control group 2, inoculated with leukemia at -4 d and total body irradiation (TBI) treatment. Control group 3, TBI treatment and reconstituted with 2 × 10(6) UCB-TNCs. Control group 4, injected with PBS subcutaneously, TBI treatment and reconstituted with UCB-TNCs with platelet transfusion. Control group 5, inoculated with leukemia, injected with PBS subcutaneously, TBI treatment and reconstituted with UCB-TNCs with platelet transfusion. Experiment group 1, injected with KGF subcutaneously, TBI treatment and reconstituted with UCB-TNCs with platelet transfusion. Experiment group 2, inoculated with leukemia, injected with KGF subcutaneously, TBI treatment and reconstituted with UCB-TNCs with platelet transfusion. The survival status, pathohistological changes, splenic lymphoid cell subsets and thymic output post-UCBT were compared between groups.
RESULTS: The survival time of control group 1 was (11.1 ± 1.5) days and all died of leukemia. The survival time of control group 2 was (11.5 ± 2.5) days and all died of aplasia. Five of 12 mice of control group 3 survived for 100 days and 7 mice died of visceral hemorrhage. Four of 12 mice of control group 5 survived for 100 days and 8 mice died of leukemia with a survival rate of 33.3%. Nine of 12 mice of experiment group 2 survived for 100 days and 3 mice died of leukemia with a survival rate of 75.0%. The survival was prolonged in experiment group 2 mice as compared with that of control group 5 mice (χ(2) = 4.996, P = 0.0254). The splenic T, NK and B cell counts in control group 4 mice at +35 d were (9.32 ± 0.48) × 10(6), (1.59 ± 0.11) × 10(6) and (18.74 ± 2.01) × 10(6) respectively. While in group 6 mice at +35 d were (13.20 ± 1.14) × 10(6), (1.75 ± 0.12) × 10(6) and (20.36 ± 0.86) × 10(6) respectively. The counts of T cell and NK cell of group 6 were higher than those of group 4 (both P < 0.05). The level of signal joint T-Cell receptor excision circles (sjTRECs) in control group 4 mice was (167 ± 17) copies per 10(5) cells while that of experiment group 1 mice (228 ± 24) copies per 10(5) cells. They were higher than that of control mice (P = 0.002).
CONCLUSION: Hematopoietic stem/precursor cells are abundant in full-term murine fetal peripheral blood. The infusion of KGF reduces the post-UCBT relapse of leukemia through the enhancement of thymic output.

PMID: 22333552 [PubMed - in process]

Ovarian Cancer Stem Cell Markers: Prognostic and Therapeutic Implications.

Cancer Lett. 2012 Feb 11;

Authors: Burgos-Ojeda D, Rueda BR, Buckanovich RJ

Abstract
Cancer stem cells are rare chemotherapy resistant cells within a tumor which can serve to populate the bulk of a tumor with more differentiated daughter cells and potentially contribute to recurrent disease. Ovarian cancer is a disease for which at the time of initial treatment we can obtain complete clinical remission in the majority of patients. Unfortunately, most will relapse and succumb to their disease. This clinical course is in line with the cancer stem cell model. In the past five years a significant amount of work has been done to identify cells with characteristics of ovarian cancer stem cells. This review will focus specifically on the markers used to define human ovarian cancer stem cells, the prognostic implications of the expression of these cancer stem cell markers in patient's primary tumors, and the potential of these cancer stem cell markers to serve as therapeutic targets.

PMID: 22334034 [PubMed - as supplied by publisher]