Transplantation of CD34+ enriched allografts in children with nonmalignant diseases: does graft manipulation necessarily result in high incidence of graft failure?
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Antigens, CD34↗
Biomedical subjects
P Lang
Publications and source records attributed to P Lang.
Correction of persistent thrombocytopenia by a boost of CD133+ selected stem cells in a patient transplanted for Wiskott-Aldrich syndrome 10 years ago.
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AC133 Antigen↗
Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective.
Children with leukemias and increasing mixed chimerism (increasing MC) after allogeneic stem cell transplantation have the highest risk to relapse. Early immunological intervention was found to be effective in these cases. To substantiate this on a defined group of pediatric acute myelogenous leukemia (AML) patients, we performed serial analysis of post transplant chimerism and pre-emptive immunotherapy in patients with increasing MC. In total, 81 children were monitored, 62 patients revealed complete chimerism (CC), low-level MC or decreasing MC. Increasing MC was detected in 19 cases. Despite early immunological intervention relapse was still significantly more frequent in patients with increasing MC (9/19) than in patients with CC, low-level or decreasing MC (8/62, P<0.005). The probability of 3-year event-free survival (EFS) was 52% for all patients (n=81), 59% for patients with CC, low-level MC, 60% for patients with decreasing MC (n=62), and 28% for patients with increasing MC (n=19, P<0.005). Patients with increasing MC who received early immunological intervention showed a significantly enhanced probability for event-free survival (pEFS 36%, n=15) compared to patients with increasing MC without intervention (pEFS 0%, n=4, P<0.05). These results prove that pediatric AML patients with increasing MC are at highest risk for relapse and that early immunological intervention can prevent relapse in these patients.
Adolescent↗
L-type and T-type Ca2+ current in cultured ventricular guinea pig myocytes.
The aim of this investigation was to study L-type and T-type Ca(2+) current (I(CaL) and I(CaT)) in short-term cultured adult guinea pig ventricular myocytes. The isolated myocytes were suspended in serum-supplemented medium up to 5 days. Using whole-cell patch clamp techniques ICaL and ICaT were studied by applying voltage protocols from different holding potentials (-40 and -90 mV). After 5 days in culture the myocytes still showed their typical rod shaped morphology but a decline in cell membrane capacitance (26 %). The peak density of ICaT was reduced significantly between day 0 (-1.6+/-0.37 pA/pF, n=9) and day 5 (-0.4+/-0.13 pA/pF, n=11), whereas peak ICaL density revealed no significant differences during culturing. The I(CaT)/I(CaL) ratio dropped from 0.13 at day 0 to 0.05 at day 5. Compared with day 0 I(CaL) the steady state inactivation curve of day 1, day 3 and day 5 myocytes was slightly shifted to more negative potentials. Our data indicate that guinea pig ventricular L-type and T-type Ca(2+) channels are differently regulated in culture.
Animals↗
Comparative analysis of chloroplast DNA variability in wild and cultivated Citrullus species.
PCR amplification and restriction site analysis of chloroplast (cp) DNA regions was used to detect inter- and intraspecific differences in the genus Citrullus. More than 55 C. lanatus and 15 C. colocynthis accessions collected from diverse geographical areas, C. ecirrhosus and C. rehmii were used. Most of the cpDNA variation within Citrullus was the result of large indels and transitions and transversions. Indels at the ndhA, trnS- trnfM and trnC- trnD regions and several substitutions at restriction enzyme sites can be used to separate C. colocynthis from the other Citrullus species. A nucleotide substitution at a restriction enzyme site at the 3' flanking region of ndhF provided a diagnostic haplotype for C. lanatus var. lanatus, the cultivated watermelon. Similarly, a nucleotide substitution at an intergenic spacer region of the trnC- trnD region resulted in a diagnostic haplotype for citron, C. lanatus var. citroides. Several C. lanatus var. citroides accessions showed the var. lanatus haplotype. C. rehmii showed almost the same haplotype as C. lanatus var. citroides with the exception of a unique insertion at a cpSSR site. Since C. ecirrhosus lacks the derived diagnostic nucleotide substitutions of C. lanatus, it is probably the progenitor of the cultivated watermelon. Intraspecific haplotypes detected within C. colocynthis were associated with geographic origin.
Base Sequence↗
Tumour cell contamination of autologous stem cells grafts in high-risk neuroblastoma: the good news?
We analysed the effect of graft-contaminating tumour cells on the long-term survival of 24 patients with high-risk neuroblastoma and found that patients whose grafts contained detectable neuroblastoma cells had a significantly higher probability of survival than did patients with no detectable tumour cells. Estimated contamination of the graft by more than 2000 tumour cells was associated with a significantly higher probability of survival than contamination with fewer tumour cells. We hypothesise that the presence of a critical number of graft-contaminating neuroblastoma cells can elicit a protective antitumour immune response after autologous transplantation.
Antigens, CD34↗
Bicêtre hospital experience with sirolimus-based therapy in human renal transplantation: the Sirolimus European Renal Transplant Study.
In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n = 42) or sirolimus (n = 41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. At 12 months, graft survival (98% sirolimus vs 93% CsA), patient survival (100% vs 98%), and incidence of biopsy-confirmed acute rejection (41% vs 38%) were similar. Serum creatinine was lower with sirolimus, significantly (P </=.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities were reported significantly more often with sirolimus, which included hypertriglyceridemia (51% vs 12%), hypercholesterolemia (44% vs 14%), thrombocytopenia (37% vs 0%), leukopenia (39% vs 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/mL. Occurrence of cytomegalovirus was comparable (14% vs 12%), but incidence of herpes simplex (24% vs 10%, P =.08) and pneumonia (17% vs 2%, P =.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs 33%). Two malignancies were observed with CsA, none with sirolimus. Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from that of CsA.
Adrenal Cortex Hormones↗
Severe recurrent cytomegalovirus disease revealed by a colocutaneous fistula in a kidney transplant recipient.
Intestinal disorders are classical complications of cytomegalovirus (CMV) infection in kidney transplant recipients (Helderman JH, Goral S. Gastrointestinal complications of transplant immunosuppression. J Am Soc Nephrol 2002: 13: 277-287). Severe ulcerative colitis that is sometimes lethal has been reported (Foucar E, Mukai K, Foucar K, Sutherland DE, Van Buren CT. Colon ulceration in lethal cytomegalovirus infection. Am J Clin Pathol 1981: 76: 788-801 and Frankel AH, Barker F, Williams G, Benjamin IS, Lechler R, Rees AJ. Neutropenic enterocolitis in a renal transplant patient. Transplantation 1991: 52: 913-914). The immunosuppressive drugs currently used, and notably mycophenolate mofetil (Cellcept), cause significant changes in the incidence, duration, and viral load of CMV infections with severe atypical forms of CMV disease (De Maar EF, Verschuuren EA, Homan vd Heide JJ, et al. Effects of changing immunosuppressive regimen on the incidence, duration and viral load of cytomegalovirus infection in renal transplantation: a single center report. Transpl Infect Dis 2002: 4: 17-24 and Perez Valentin MA, Cofan F, Sole M, et al. Atypical cytomegalovirus in renal transplantation: a new form of presentation. Nefrologia 2002: 22: 381-385). This report describes a patient who suffered from several episodes of colitis due to an unusual and late-appearing CMV infection.
Antigens, Viral↗
A prospective comparison of immune reconstitution in pediatric recipients of positively selected CD34+ peripheral blood stem cells from unrelated donors vs recipients of unmanipulated bone marrow from related donors.
Positively selected CD34(+) hematopoietic stem cells from unrelated donors (UD-HSCT) have been successfully transplanted, but little is known about immune reconstitution in this setting. Here we report a prospective comparison of immune reconstitution in recipients of UD-HSCT and of unmanipulated bone marrow from matched sibling donors (MSD-BMT). T-cell reconstitution occurred more than 100 days later in the UD-HSCT than in the MSD-BMT group. The first T cells after UD-HSCT were almost exclusively CD45RO(+) HLA-DR(+), whereas early-emerging T cells after MSD-BMT more frequently expressed CD62L, CD28, and CD25. In both groups, numbers of CD45RA(+) naive T cells increased after 180 days. After UD-HSCT, the T-cell-receptor (TCR)-repertoire was severely skewed and showed significantly reduced diversity during the first year, but only minor abnormalities were seen after MSD-BMT. TCR-diversity increased simultaneously with the number of naive T cells. In both groups, we observed transient expansions of gammadelta T cells. B cells were reconstituted more rapidly in UD-HSCT than in MSD-BMT recipients, whereas the rapidity of NK-cell reconstitution was similar in the two groups. In summary, T-cell reconstitution was slower after UD-HSCT than after MSD-BMT because of the delayed recovery of early memory-type T cells with reduced TCR-diversity, whereas naive T-, NK-, and B cells were reconstituted similarly in the two groups.
Adolescent↗
Successful unrelated allogeneic stem cell transplantation after treatment of lymphoid blast crisis CML with imatinib and imatinib-containing conditioning regimen in a 16-year-old male.
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Adolescent↗
Intercontinental genetic divergence of Castanea species in eastern Asia and eastern North America.
Castanea is one of the many plant genera with a disjunct distribution pattern between eastern Asia and eastern North America. Five species from three sections of the genus were investigated to examine genetic divergence between eastern Asian and eastern North American species. A total of 62 native populations were sampled for allelic variation at isozyme loci. The Chinese chestnut C. mollissima had the highest genetic variability, while the American C. dentata had the lowest genetic variability. The highest intracontinental genetic identities were observed between the Allegheny and Ozark chinkapins (0.931) and between C. mollissima and C. seguinii (0.870), while lower identities were detected between the American C. pumila and C. dentata (0.720-0.729). In intercontinental comparisons, genetic identities of 0.505, 0.495 and 0.507 were observed between the American chestnut and the Chinese C. mollissima, C. seguinii and C. henryi, respectively, whereas the Ozark chinkapin C. pumila var. ozarkensis had lower identities of 0.469, and 0.435 with C. mollissima and C. seguinii, respectively, but a slightly higher identity of 0.520 with C. henryi, the Chinese chinkapin. Divergence times were estimated at 10-13 million years before present between C. dentata and C. mollissima, and C. pumila var. ozarkensis and C. henryi.
Biological Evolution↗
[The benefits of new immunosuppressive treatments in adult kidney transplantation].
NEW KNOWLEDGE: Over the last few years, improved knowledge of the immunological mechanisms underlying transplant rejection have resulted in the development of new immunosuppressive agents capable of selectively blocking various steps of the immune response. NEW MOLECULES: The review focuses on new immunosuppressive drugs that have been developed for clinical use in renal transplantation and mechanism of action, advantages and side effects will be discussed for each of them. Neoral is a cyclosporin microemulsion, characterized by more consistent absorption. Tacrolimus shares with cyclosporin an ability to inhibit calcineurin but presents some differences. Mycophenolate mofetyl selectively inhibits purine synthesis and lymphocyte proliferation; it is easy to use and has been found effective in large clinical trials. Rapamycin and RAD are two related molecules that inhibit signal transduction by cytokines to T-cells, their use in transplant therapy remains to be determined. Anti-interleukin-2 receptor antibodies are also reviewed; they are easy to use and have been found effective. NEW STRATEGIES: These new immunosuppressive drugs provide new approaches in transplant therapy to improve their efficacy and safety.
Adult↗
[Giant hemangioma of the tongue: combined use of perioperative blood conservation procedures].
A giant hemangioma of the tongue was resected in a 16-year-old otherwise healthy young man (ASA I). Despite a total blood loss of 4,300 ml, corresponding to 105% of the patients intravascular blood volume, no allogeneic red blood cells had to be transfused intraoperatively. Besides minimization of intraoperative blood loss with preoperative alcohol injections into the tumor, ligation of large tumor-perfusing arteries, application of fibrin glue, skillful surgical technique, positioning of the surgical field above the level of the heart, controlled hypotension and maintenance of normothermia, acute normovolemic hemodilution (augmented by preoperative administration of recombinant human erythropoetin - rhEpo) and autotransfusion of lost blood were used for recovery of autologous blood. Under the protection of hyperoxia, a decrease of the hemoglobin (Hb) concentration to 4.2 g/dl was bridged by extreme normovolemic hemodilution. No signs of immanent or manifest tissue hypoxia were encountered. Retransfusion of autologous red blood cells was only started when surgical control of bleeding was achieved. Additionally a total of 4 units of fresh frozen plasma were infused for stabilization of plasma coagulation. After a 9-hour surgical duration, the patient was transferred to the intensive care unit, normotensive (with low-dose infusion of norepinephrin) and normothermic with a Hb concentration of 5.6 g/dl. In the face of an increasing lactacidosis 2 units of packed red blood cells were transfused on post surgical day 1.
Adolescent↗
[Detection and treatment of depressive symptoms in nursing home patients. An interdisciplinary challenge for the geriatric physician and nursing personnel].
40% of nursing home patients have depressive symptoms and 20% have a diagnosis of depression according to DSM-IV or ICD-10 classification. Depressive Symptoms in nursing home patients are underdiagnosed and undertreated. We report a triple pharmacological, psychosocial and staff teaching intervention in a nursing home based on the Resident Assessment Protocols (RAP) trigger mechanism of the Resident Assessment Instrument (RAI) that was able to significantly and persistently reduce the prevalence of depressive symptoms in this population.
Activities of Daily Living↗
Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in children.
We present a clinical scale method for immunomagnetic separation of CD56+ donor natural killer cells for adoptive immunotherapy of pediatric leukemias after allogeneic transplantation. This time-saving and partially automated procedure employed CD56+ selection followed by CD3+ depletion, resulting in a median purity of 98.6% NK cells and a four-log depletion of T cells. The enriched NK cells demonstrated high cytotoxic activity against K562 target cells and fresh leukemic blasts with low HLA class I expression, which could be further enhanced by IL-2 stimulation. Lysis of NK-insensitive leukemic cells with high HLA class I expression could also be demonstrated via ADCC. Due to the high degree of T cell depletion, alloreactive proliferation in mixed lymphocyte cultures and response to T cell-specific mitogen stimulation was profoundly decreased. Our results suggest that, even in the case of mismatched donors, infusions of donor NK cells with extremely low T cell content may be a promising treatment option for leukemic minimal residual disease after allogeneic transplantation without risk of inducing severe GVHD.
CD56 Antigen↗
Isolation and transplantation of highly purified autologous peripheral CD34(+) progenitor cells: purging efficacy, hematopoietic reconstitution and long-term outcome in children with high-risk neuroblastoma.
We have investigated the purging efficacy of positive selection of autologous mobilized CD34(+) peripheral stem cells in 22 children with high-risk neuroblastoma. CD34(+) cell selection was performed using the method of magnetic-activated cell sorting (MACS). The median purity of the CD34(+) cells post selection was 97.6% (range 81.7-99.7). For detection of contaminating neuroblastoma cells before and after CD34(+) selection, the chimeric anti-disialoganglioside GD2 antibody delta ch 14.18 was used. Prior to positive selection, various numbers of contaminating neuroblastoma cells were found in 17 patients. After positive CD34(+) cell selection, low numbers of neuroblastoma cells were only detectable in four patients. In 18 patients, high-dose chemotherapy was performed and the isolated CD34(+) cells were reinfused. In all patients, a rapid neutrophil recovery was seen with a median time to reach 0.5 x 10(9)/l neutrophils of 12 days (range 8-24 days). Nine of the 18 patients are free of progression with a median follow-up of 55 months (range 45-70 months). Two patients are alive with relapse, six patients died due to progression or relapse and one patient died due to secondary AML 10 months after transplant while in remission from neuroblastoma. In summary, we show that, through a highly effective positive selection method, a high purging efficacy can be obtained without compromising the hematopoietic reconstitution capacity of the graft.
Antigens, CD34↗
Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery.
As recently reported, children having T cell-depleted peripheral blood stem cell transplantation (PBSCT) might be at increased risk for the development of drug resistance. To investigate if delayed immune recovery was a potential risk factor, the recovery of the CD3(+), CD4(+), CD8(+) and CD19(+) cells was related retrospectively to genotypic detected resistance development in three pediatric patients with ganciclovir (GCV)-resistant human cytomegalovirus (HCMV)-infection out of 79 receiving allogeneic PBSCT. Selected control groups consisted of HCMV-seronegative patients without any infection (A, n = 8), asymptomatic infected patients with viral leuko- and plasmaDNAemia (B, n = 4) and patients with HCMV-disease (pneumonia) (C, n = 3). Patient No. 1 with very early resistance development exhibited a rapid immune recovery with higher T cell counts than in group A. Immune recovery of patient No. 2 was delayed, as also observed in groups B and C. Patient No. 3 showed an immune recovery comparable to group A. Resistance developed before (No. 2) or during (Nos 1 and 3) the recovery of the relevant CD3(+), CD4(+), CD8(+) lymphocytes. GCV-resistance development did not necessarily coincide with delayed immune recovery, but appeared in all three cases in the early phase of immune recovery (range: day +44 to day +95). Therefore, children seem to be at special risk for resistance development in the early phase after transplantation before immune cells have recovered. These results suggest that GCV treatment of an HCMV infection in the early posttransplant phase of children after T cell-depleted PBSCT/BMT should promote more stringent resistance screening.
Antigens, CD↗
[Risk factors for cutaneous wart onset in transplant recipients].
INTRODUCTION: Transplant recipients are at increased risk for cutaneous warts. We have investigated the delay of their onset warts and some possible risk factors for their occurrence. PATIENTS AND METHODS: Clinical data were summarized on a standard question and examination sheet. Warts were diagnosed on clinical grounds and course duration assessed on patients' report. Immunosuppressive therapy and HLA group were collected from clinical transplantation records. An actuarial curve was used to evaluate the delay of onset of warts. To compare associated risk factors among the two groups (patients with warts and patients without warts) at 1 year and 3 years following transplant, single variate analysis was performed. RESULTS: At the time of transplant, the prevalence of warts was 16 p. 100. It was increased with the duration of immunosuppression: 23 p. 100 at 1 year, 35 p. 100 at 3 years, 45 p. 100 at 5 years and 54 p. 100 at 7 years. Warts were multiple and principally localized on the hands. Transplant recipients without cutaneous warts 3 years after transplant had less intensive immunosuppressive therapy than the group with cutaneous warts. No association was found between age, sex, HLA markers, actinic keratosis and wart onset. DISCUSSION: The prevalence of warts increases with the duration of transplantation. Cutaneous warts are generally multiple and have a chronical course without spontaneous remission. More intensive immunosuppressive therapy increases their occurrence. This trial cannot evaluate the association between carcinoma and warts. On the basis of our study, there is no relationship between actinic keratosis and warts, nor HLA markers and warts.
Adult↗