Objective To investigate the possible occurrence of early thymic failure and premature senescence of naïve and memory T-cells in patients with axial spondyloarthritis (aSpA). Methods Prospective, cross-sectional study of consecutive patients with aSpA (n=51), rheumatoid arthritis (RA, n=51) and healthy controls (HCs, n=50). Demographic, clinical and laboratory parameters were collected in all patients and we isolated naïve (CD45RA⁺) and memory (CD45RO⁺) CD4⁺ and CD8⁺ T-cell subsets by MACS technology. T-cell receptor rearrangement excision circle (TREC) and telomere length were measured by real-time PCR. We used TRECs as a surrogate for thymus function and telomere length as an indicator of cellular senescence. Telomerase activity was analysed with the Telomeric Repeat Amplification Protocols. Results We observed a premature decline of thymic output in patients with aSpA and patients with RA compared with HCs as indicated by a reduction of TREC levels in naive T-cells (aSpA: age adjusted regression coefficient (reg_coeff) for CD4⁺CD45RA⁺ T-cells −2.566, p=0.023; RA reg_coeff=−2.844, p=0.008). Telomere length of all CD4⁺ and CD8⁺ T-cell subsets was reduced in young patients with aSpA compared with HCs, whereas data for patients with RA were comparable with HCs. Telomerase activity was inversely correlated with telomere length in HCs (correlation coefficient (cor_coeff)=−0.532, p<0.001) but not in patients with aSpA (cor_coeff=−0.056, p=0.697) and RA (cor_coeff=−0.003, p=0.982). Conclusions Our data indicate an age-inappropriate shrinkage of thymic output, an inappropriate shortening of telomeres in young patients with aSpA and an impaired telomerase enzyme in patients with aSpA and RA.

Summary: Immune reconstitution is critical for the long‐term success of haematopoietic stem cell transplantation (HSCT). We prospectively analysed immune reconstitution parameters after transplantation of autologous (group 1; n = 10) and allogeneic (group 2; n = 12) highly purified CD34⁺ peripheral blood stem cells (PBSC) and unmanipulated allogeneic bone marrow (BM) (group 3; n = 9) in children. Median follow‐up after HSCT was 56 (group 1), 61 (group 2), and 40·5 months (group 3). Median CD34‐cell dose transplanted in the three groups was 9·4 × 10⁶/kg, 20·3 × 10⁶/kg, and 4·25 × 10⁶/kg recipient's body weight (BW) respectively. Complete haematopoietic engraftment was seen in all patients without any significant differences between the three groups. T‐cell reconstitution at 6 months was significantly delayed in autologous peripheral blood stem cell transplantation (PBSCT) compared with allogeneic BM transplantation (P < 0·028) and allogeneic PBSCT (P < 0·034). At 3 months after transplantation numbers of CD56⁺/3⁻ natural killer cells were higher in the allogeneic PBSC group (P < 0·01) compared with the BM group. The numbers of proven bacterial and viral infections were equally distributed between the three groups. In conclusion, recipients of allogeneic highly purified CD34⁺ PBSC or unmanipulated BM have higher lymphocyte subset counts at 6 months after transplantation than recipients of autologous CD34‐selected PBSC. Infection rates and outcome, however, were not significantly different.

Background The administration of intensive, risk adapted multiagent chemotherapy has markedly improved the event-free survival in childhood acute lymphoblastic leukemia and Non-Hodgkin's lymphoma. Current treatment protocols may achieve complete remission rates of more than 95% and event-free survival rates of approximately 70% in non-B-acute lymphoblastic leukemia/non-B-Non-Hodgkin's lymphoma patients. Due to a higher proliferation rate and aggressiveness of B-cells treatment of B-acute lymphoblastic leukemia/ B-Non-Hodgkin's lymphoma must be more intensive, but can be shorter to attain similar event-free survival rates. Methods Between 1984 and 1993 79 primarily admitted patients up to 18 years of age (range 0.6-17.9 years) received therapy according to the treatment protocols ALL A 84, ALL 86, NHL 86, ALL 90 and NHL 90 of the Berlin-Frankfurt-Münster Study Group. Intensive phases of treatment were given on an inpatient basis with maximum supportive care in order to achieve the prescribed doses. Results Median follow-up time from diagnosis is now 8 years (range 40 to 157 months) with a probability of event-free survival of 92% for the entire group. Conclusion Multiagent chemotherapy tailored to the individual risk profile of each patient but given in the prescribed dose is currently the mainstay to achieve high complete remission rates with the aim to cure most acute lymphoblastic leukemia/Non-Hodgkin's lymphoma patients. The administration of intensive supportive care is important for the achievement of complete drug dosage and for the reduction of therapy-related toxicity. Hintergrund Durch den Einsatz intensiver risikoadaptierter Polychemotherapie hat sich das ereignisfreie Überleben bei akuten lymphoblastischen Leukämien und Non-Hodgkin-Lymphomen im Kindesalter deutlich verbessern lassen. Derzeitige Behandlungsprotokolle erzielen komplette Remissionen in mehr als 95% und ereignisfreies Überleben in ungefähr 70% der Patienten mit akuter Non-B-lymphoblastischer Leukämie und Non-B-Non-Hodgkin-Lymphom. Eine intensivere, jedoch kürzere Therapie ist aufgrund der höheren Proli ferationsrate maligner B-Zellen bei der Behandlung der aggressiveren akuten B-lymphoblastischen Leukämie und des B-Non-Hodgkin-Lymphom's nötig, um ähnliche Therapieergebnisse zu erzielen. Patienten und Methoden Zwischen 1984 und 1993 wurden 79 erstaufgenommene Patienten bis zum 18. Lebensjahr (0,6-17,9 Jahre) entsprechend den Behandlungsprotokollen ALL A 84, ALL 86, NHL 86, ALL 90 und NHL 90 der BFM-Arbeitsgruppe behandelt. Die Patienten wurden während intensiver Behandlungsphasen stationär aufgenommen und erhielten bei maximaler supportiver Therapie genau die vom Protokoll vorgeschriebenen Medikamentendosen. Ergebnisse Die mediane Nachbeobachtungszeit beträgt seit Diagnosestellung 8 Jahre (range 40-157 Monate) mit einer Wahrscheinlichkeit des ereignisfreien Überlebens von 92%. Schlußfolgerung Die dem individuellen Risikoprofil des Patienten angepaßte und ohne Dosisreduktion verabreichte zytostatische Polychemotherapie ist derzeit immer noch der wesentlichste Faktor, um hohe komplette Remissionsraten mit dem Ziel der Heilung zu erreichen. Der begleitende Einsatz intensiver supportiver Therapie ist unerläßlich, um die vorgeschriebene Behandlungsdosis bei gleichzeitiger Reduktion therapiebedingter Nebenwirkungen zu gewährleisten.

For patients with mucopolysaccharidosis type IH (MPS1-H; Hurler syndrome), early allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice. One boy and one girl aged 20.5 and 22 months, respectively, with MPS1-H received a conditioning regimen consisting of thiotepa, fludarabine, treosulfan, and ATG. Grafts were peripheral blood stem cells from unrelated donors (10/12 and 11/11 matched), that were manipulated by CD3/CD19 depletion and contained 20.3 and 28.2 × 10(6) CD34+ cells/kg body weight, respectively. Both patients achieved stable hematopoietic engraftment and stable donor chimerism. Neither acute or chronic graft-versus-host disease (GVHD) nor other severe transplant-related complications occurred. At a follow-up of 48 and 37 months, both patients are alive and well with normal levels of α-L-iduronidase and have made major neurodevelopmental progress. Treosulfan-based conditioning offers the advantage of reduced toxicity; the use of unrelated CD3/CD19-depleted peripheral stem cell grafts allows transfusion of high CD34+ cell numbers together with a "tailored" number of CD3+ cells as well as engraftment facilitating cells in order to achieve rapid hematopoietic engraftment while reducing the risk of graft rejection and GVHD. This regimen might be an additional option when unrelated donor HSCT is considered for a patient with MPS1-H