[show abstract][hide abstract] ABSTRACT: Background
Cord blood transplantation (CBT) is accepted therapeutic method in transplantology since 1988. The first isolated CBT was performed on 12 October 2000 in Poznań.Objective
Analysis of results of CBT in Polish pediatric centers.Patients and methodsA total numer of 19 patients (5 female, 14 male), aged 0.1–10 years (median 4.3 yrs) transplanted with cord blood between 2000–2011 in Polish pediatric centers. The initial diagnosis was: acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 1), myelodysplstic syndrome (n = 2), Wiskott-Aldrich syndrome (n = 3), Fanconi anemia (n = 2), adrenoleukodystrophy (n = 1), Langerhans cell histiocytosis (n = 1), chronic granulomatous disease (n = 1), Kostmann syndrome (n = 1), Sandhoff syndrome (n = 1). Pre-transplant conditioning was myeloablative in 9 patients and reduced-intensity in 10 patients. The source of cord blood was family donor in 8 cases or unrelated donor in 11 cases. Histocompatibility 6/6 HLA between donor-recipient was present in 10 cases.Results10/19 (52.6%) children stay alive, median survival 3.1 years (95%CI = 1.4–4.7), probability of 2-year survival was 0.409 ± 0.133. The cause of death was primary graft failure (n = 2), infectious complications (n = 3) or relapse (n = 4). Two children with primary graft failure had subsequent haploidentical transplantation. In multivariate analysis, generalized documented infection was the only predictive adverse factor of overall survival.ConclusionCBT is an important therapeutic option for patients lacking matched donor, offering positive outcome for a half of patients.
[show abstract][hide abstract] ABSTRACT: In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.
[show abstract][hide abstract] ABSTRACT: Intravenous immunoglobulins (IVIG) remain an important part of both causative and supportive therapy in pediatric oncohematology and after hematopoietic cell transplantation. The article presents actual recommendations on the use of IVIG based on personal experience and on UK guidelines published in 2008. IVIG substitution remains an important part of therapy in children with delayed immune reconstitution after hematopoietic stem cell transplantation (post transplants from alternative donors and in the course of acute and chronic Graft versus Host Disease). IVIG play a significant role in the immunomodulation of children with autoimmune disorders, i.e. primary immune thrombocytopenia.
Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 06/2011; 30(180):405-8.
[show abstract][hide abstract] ABSTRACT: After stem cell transplantation, human patients are prone to life-threatening opportunistic infections with a plethora of microorganisms. We report a retrospective study on 116 patients (98 children, 18 adults) who were transplanted in a pediatric bone marrow transplantation unit. Blood, urine and stool samples were collected and monitored for adenovirus (AdV) DNA using polymerase chain reaction (PCR) and real-time PCR (RT-PCR) on a regular basis. AdV DNA was detected in 52 (44.8%) patients, with mortality reaching 19% in this subgroup. Variables associated with adenovirus infection were transplantations from matched unrelated donors and older age of the recipient. An increased seasonal occurrence of adenoviral infections was observed in autumn and winter. Analysis of immune reconstitution showed a higher incidence of AdV infections during periods of low T-lymphocyte count. This study also showed a strong interaction between co-infections of AdV and BK polyomavirus in patients undergoing hematopoietic stem cell transplantations.
Archives of Virology 12/2010; 155(12):2007-15. · 2.03 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of our study was to compare the results of unrelated donor (UD) peripheral blood stem cell transplantation versus UD bone marrow transplantation and to analyze the impact of infused CD34(+) and CD3(+) cell doses on survival and incidence of severe graft-versus-host disease (GVHD) in 187 children who underwent UD hematopoietic cell transplantation with the use of in vivo T cell depletion (antithymocyte globulin or CAMPATH-1H). HLA typing was performed at the "high-resolution" level. Patients receiving > or =10 x 10(6) CD34(+) cells/kg and > or =4 x 10(8) CD3(+) cells/kg had better overall and disease-free survival. Multivariate analysis has shown that both infused CD34(+) cell dose <10 x 10(6)/kg and CD3(+) cell dose <4 x 10(8)/kg were independent risk factors for mortality (relative risk [RR] 1.8 and 1.71, P = .009 and .016, respectively). Regarding disease-free survival, multivariate analysis has revealed another independent risk factor for poor outcome apart from the 2 earlier-mentioned cell doses, which was the use of donors mismatched at 2 HLA antigens or 3 HLA allele/antigens (RR 2.5, P = .004). In age groups 0-10 years and 10-20 years, CD34(+) cell doses higher than the age-adjusted median dose clearly favored survival. Higher infused doses of CD34(+) and CD3(+) cells did not result in an increased rate of severe GVHD. The use of mismatched donors was the only independent risk factor for the incidence of severe acute GVHD (RR 2.2, P = .046). The report demonstrates for the first time in a pediatric cohort, that higher doses of transplanted CD34(+) and CD3(+) cells lead to an improved survival without an increased risk of severe GVHD. The study findings may be limited to the population of patients receiving in vivo T cell depletion, which is now broadly used in unrelated donor setting in Europe.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2010; 16(10):1388-401. · 3.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: Introduction: Galactomannan (GM) is a component of Aspergillus cell wall used as diagnostic marker for invasive aspergillosis (IA) in immunocompromised patients.
The aim of study: The study presents the results of 2-years GM testing in patients treated in the Department of Paediatric Haematology, Oncology and Bone Marrow
Transplantation of Wroclaw Medical University.
Material and methods: Blood samples taken weekly from high risk patients were examined using immunoenzymatic method. A total number of 108 patients, incl. 21
adults and 87 children were tested. Ninety-eight patients underwent hematopoietic stem cell transplantation, and 10 were on intensive chemotherapy.
Results: Positive results (GMI≥0.5) were found in 10 patients (10% of all examined),among them 3 patients presented with history of aspergillosis, whereas the remaining
7 patients were treated for proven, probable, or possible aspergillosis. Among patients with negative GM results, two were classified as having possible aspergillosis.
Fungal lesions were most frequently found in lungs, and in two patients also in liver and spleen. Only one patient showed sinus aspergillosis. Test sensitivity was estimated
for 83%, when single positive results were considered, and 53%, when at least two consecutive positive results were required.
Conclusions: GM represents highly specific marker of IA in hematologic patients, however it should be used together with classical mycology, as well as clinical picture
and risk factors analysis.
[show abstract][hide abstract] ABSTRACT: To present results of megachemotherapy and autologus hematopoietic stem cell transplantation in children with Ewing sarcoma in 4 Polish pediatric transplantation centres.
Between the years 1995-2007 autologous stem cell transplantation was performed in 54 patients (25 girls and 29 boys) with Ewing sarcoma. 26 patients were in complete remission before megachemotherapy, 23 were in partial remission, 3 patients had progression of the disease and the status of 2 patients was unknown. 41 children received busulfan 16 mg/kg and melphalan 140 mg/m(2), 8 children carboplatin 1500 mg/m(2), VP-16 40 mg/kg, melfalan 160 mg/m(2) and 5 children other megachemotherapy protocols.
Probability of survival of patients after transplantation, in complete remission is 0,79 with median 35 months of observation time. For patients after transplantation in partial remission probability of survival was 0,25 with median observation time of 14 months. Patients in progressive disease died 1,3 and 7 months after transplantation. 32 children are alive and 22 patients died, 21 of them due to disease progression.
1. Megachemotherapy and autologous hematopoietic stem cell transplantation is a safe therapy in patients with high risk Ewing sarcoma in complete remission. 2. Proportion of patients with sustained remission after transplantation in greater as compared to the published data related to high risk group without megachemotherapy. 3. According to our data megachemotherapy did not improve outcome in patients with partial remission of the disease.
Medycyna wieku rozwojowego 02/2008; 12(4 Pt 2):1069-73.
[show abstract][hide abstract] ABSTRACT: Twenty-one children with high-risk Ewing's tumor received high-dose chemotherapy with a PBSCT. Aim of the study was evaluation of efficiency and safety of this procedure. All but three patients have meta-static disease at presentation. There were 11 females and the median age at diagnosis was 12 yr (range 4.5-18 yr). Megachemotherapy consisted of melphalan 140 mg/m2/busulfan 16 mg/kg in 12 patients, melphalan 140 mg2/treosulfan 10.0 g/m2 in two patients and melphalan with other drugs in seven patients. Eight of 11 patients transplanted in CR survived with a median follow-up 24 month (range 14-60) and probability of 2-year OS is 0.68 and DFS is 0.63. There was no severe regimen-related toxicity in this group. Children transplanted without remission died: Two of them due to transplant related causes and eight had progression of disease in a median time 7 month after PBSCT. Megachemotherapy with PBSCT is a safe procedure in children with Ewing's sarcoma in remission. Autologos transplantation in children with metastatic Ewing's sarcoma seems to improve their outcome. Patients with Ewing's sarcoma, resistant to conventional therapy and with recurrent disease did not benefit from megachemotherapy. New approaches such as anti-tumor vaccination or using of imatinib are reasonable to introduce in patients with relapsed or resistant to therapy Ewing's tumor.
[show abstract][hide abstract] ABSTRACT: From January 1st 1995 to March 31st 2003 a total of 51 autologous stem-cell transplantations (auto-HSCT) in 49 children with non Hodgkin lymphomas (NHL) were carried out in the transplantation centres of the Polish Pediatric Group for Treating Leukemias and Lymphomas (PPGLBC). In 2 patients the transplantations were carried out twice. The age of children at the moment of the transplantation ranged from 2.8 to 17.3 years (median 10.0), with higher representation of boys than girls. Twenty eight of the procedures were carried out in children with the diagnosis of B-cell non Hodgkins lymphoma (B-NHL), eight--in children with non B-cell non Hodgkins lymphoma (NB-NHL) and thirteen--in patients with anaplastic large cell lymphoma (LCAL). 16 procedures were performed in children who at the moment of transplantation were in their first complete remission (CR), another 16 were carried out while in their 2nd and 3rd CRs, and 17 transplants were performed at partial remission (PR). In addition, two children received transplants in the phase of the disease relapse. In most cases (44) the BEAM protocol was applied as megachemotherapy. In 49 procedures peripheral blood was the source of stem-cells, in one--bone marrow, in one--bone marrow + peripheral blood. The number of CD34/kg cells transplanted ranged from 1.2 x 10(6) to 8.0 x 10(6) (median 4.2 x 10(6)). Hematologic reconstitution occurred in all but one patient who died on the 10th day from HSCT. 42 out of the 49 children (87%) survived with the observation time ranging from 1 to 94 months (median 47 months). During the observation time, 34 of children were in CR. In 15, disease relapses or progression were noted within the time ranging from 3 to 22 months from HSCT (median 6 months). Seven children died (14%) including 5 due to relapse. Expected overall survival (OS) at 5 years from transplantation for the whole group of patients was 0.85 and varied only slightly for individual categories of NHL. The probability of 5-year disease-free survival (DFS) for the whole group was 0.67 and was the highest in B-NHL (0.84) and was much lower in LCAL and in NB-NHL, 0.5 and 0.47 respectively. Our results suggest that BEAM megachemotherapy with autologous transplantation in children with NHL is a safe procedure, which at the same time improves the results of standard treatment, especially in children with NHL primary resistant to chemotherapy.
[show abstract][hide abstract] ABSTRACT: Late effects following haematopoietic stem cell transplantation occur both in children and adults. Endocrine impairment may cause abnormal growth velocity and impaired growth in children.
To assess the influence of preparative regimen-high dose chemotherapy and/or cranial irradiation as risk factors for growth impairment.
30 children underwent haematopoetic stem cell transplantation (19 girls, 11 boys) aged 2-20 years, with autologous (N=9) or allogeneic (N=21) maneuver. 14 children received cranial irradiation prior to grafting: 18 Gy (N=10) and 24 Gy (N-4), high doses chemotherapy included Busulfan/Melphalan (N=6), Cyclophosphamide/Busulfan/ Etoposide (N=6) and total body irradiation with 12 Gy (N=2). Thyroid function was evaluated prior to and after grafting. Growth hormone secretion with standard provocative test were analyzed. Bone age was estimated. State of nutrition 12 to 5 months before and after transplantation, WLI (weight-for-length index) and BMI (body mass index) were evaluated. Abnormal growth velocity denotes decrease > or =1 SD.
1. Cyclophosphamide statistically significantly blunted growth velocity 4 (n=28; p=0.046; r=0.4). 2. Significant correlation (n=28; p=0.0184; r=0.45) was found between abnormal gonadal function and Busulfan. 3. Cranial irradiation prior to preparative regimen impaired growth more significantly than high dose chemotherapy (n=28; p=0.0044). 4. Evaluated WLI determined short stature after transplantation (n=26; p<0.001).
Hematopoietic stem cell transplantation causes long term endocrine complications especially impaired growth.
[show abstract][hide abstract] ABSTRACT: Posttransplant morbidity and clinical outcome in children with advanced neuroblastoma (NBL) who underwent megachemotherapy followed by HSCT were investigated.
In the study 73 children with advanced NBL treated in four Departments of Paediatric Haematology and Oncology in Lublin, Kraków, Wrocław and Bydgoszcz from 1995 to 2004 were analysed. Median age of children was 4.9 years (range 1.8 to 15). Reinfusion of CD34 cells followed myeloablative chemotherapy with Busulfan / Melfalan in 58 patients; Treosulfan / Melfalan in 2 patients; Melfalan / VP16/ Carbo in 9 patient, Melfalan alone in 3 patients and Thiotepa /CTX/ Carbo in 1 patient. Stem cells from peripheral blood were used in 57 cases, bone marrow in 10 patients, bone marrow and peripheral blood in 6 patients.
41/73 (56%) children are alive with median follow up 12 months (range 3 to 68 months), 29 children are in complete remission (CR), 12 patients are in partial remission (PR). 32/73 (44%) children died, 26 of them due to progressive disease; six children died due to posttransplantation complications. Overall survival (OS) at median observation time 12 months is 0.65; disease free survival (DFS) is 0.58. Probability of 5-year OS and DFS in the group of children transplanted in first partial/complete remission are 0.42 and 0.4 respectively.
Treatment with megachemotherapy followed by autoHSCT in patients with advanced neuroblastoma has not many adverse effects. Probabilities of 5-year OS and DFS are higher in the group of transplanted children in 1 partial/complete remission than in children transplanted after relapse.
[show abstract][hide abstract] ABSTRACT: AIM OF THE STUDY was to present the experience of four Polish transplantation centres (Wroclaw, Bydgoszcz, Kraków and Lublin) with use of megachemotherapy (MCT) and autologous hematopoietic stem cell transplantation (autoHSCT) in children with high risk solid tumours.
Between 1994 and 2005 in 67 patients, whose age ranged form 1.5 to 20 years, 74 procedures of megachemotherapy and auto HSCT were performed. 25 children were treated for Ewing Sarcoma, 13 for rhabdomyosarcoma embryonale (RMS), 7 for germinal tumours, 6 for medulloblastoma, 4 for PNET, 4 for Wilm's tumours, 2 for glioblastoma and single patients with mesenchymoma, astrocytoma, ependymoma, angioblastoma, carcinoma ovarian and carcinoma embryonale glutei. Most common megachemotherapy protocols consisted of: Melphalan, Etopozyd i Carboplatin (MEC)--applied in 24 children and Busulfan plus Melphalan (Bu Mel) administered in 19 patients. In 29 children MCH was introduced in first complete remission, in 14 the procedure was performed in second or subsequent remission and 24 patients did not achieve remission before megachemotherapy was started.
30 children are alive (44%), 28 of them in complete remission of disease. 23 out of 29 (79%) patients were transplanted in first complete remission and median observation time in that group is 29 months (range 2-74 months). Only 5 out of 38 children transplanted in second complete remission or without complete remission survived. 39 patients relapsed at a median time 11 months after MCT and 37 of them subsequently died of disease at a median time of 16 months. One toxic death was noted--it was a boy, transplanted with progressive disease.
1. Megachemotherapy with autologous stem cell can rescue children with high risk solid tumours. It is a safe procedure especially when performed in remission. 2. Children with resistant or relapsed solid tumours are unlikely to benefit from megachemotherapy.