Bone marrow aplasia following donor lymphocyte infusion in 4-year-old patient with chronic granulomatous disease after allogeneic stem cell transplantation: case report.

Donor lymphocyte infusion (DLI) is typically used in 3 clinical situations: therapeutically for proven relapse of malignancy, prophylactically in patients with high-risk of relapse, and in case of mixed chimerism. Mixed chimerism, which occur after transplantation can be a sign of possible rejection. In case of increased mixed chimerism, immunotherapy with donor lymphocyte infusions could reverse this process. After DLI, both acute and chronic graft-versus-host disease and marrow aplasia are well-known toxicities. In this paper, we present a case report of young patient with chronic granulomatous disease (CGD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with successful immunotherapy following mixed chimerism, which was complicated by bone marrow aplasia that required a second stem cell infusion. DLI seems to be an effective and highly promising treatment method of transplant rejection in patients with CGD but can induce bone marrow aplasia and may require a second stem cell infusion.

Matched sibling versus matched unrelated allogeneic hematopoietic stem cell transplantation in children with severe acquired aplastic anemia: experience of the polish pediatric group for hematopoietic stem cell transplantation.

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.

[Megachemotherapy and autologous stem cell transplantation in children with Ewing sarcoma - Polish experience]. / Megachemioterapia i autologiczne przeszczepienie hematopoetycznych komorek macierzystych u dzieci z miesakiem ewinga-doswiadczenia Polskie.

AIM: To present results of megachemotherapy and autologus hematopoietic stem cell transplantation in children with Ewing sarcoma in 4 Polish pediatric transplantation centres. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Megachemotherapy and autologous hematopoietic stem cell transplantation in children with solid tumours excluding neuroblastoma--experience of Polish paediatric centres]. / Megachemotherapia i przeszczepianie autologicznych hematopoetycznych komórek macierzystych u dzieci z guzami litymi innymi niz neuroblastoma--doswiadczenia polskich osrodków pediatrycznych.

UNLABELLED: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[High-dose therapy followed by auto HSCT in children--with advanced neuroblastoma in four transplant centres in Poland]. / Megachemotherapia z autologicznym przeszczepieniem komórek krwiotwórczych u dzieci z neuroblastoma wysokiego ryzyka w 4 dzieciecych osrodkach przeszczepiania szpiku hostnego w Polsce.

AIM OF THE STUDY: Posttransplant morbidity and clinical outcome in children with advanced neuroblastoma (NBL) who underwent megachemotherapy followed by HSCT were investigated. PATIENTS AND METHODS: In the study 73 children with advanced NBL treated in four Departments of Paediatric Haematology and Oncology in Lublin, Kraków, Wroclaw 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. RESULTS: 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. CONCLUSIONS: 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.

Megachemotherapy followed by autologous stem cell transplantation in children with Ewing's sarcoma.

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.

Cytomegalovirus (CMV) infections in children undergoing hematopoetic stem cell transplantation.

Cytomegalovirus (CMV) is one of the major causes of morbidity and mortality after hematopoetic stem cell transplantations (HSCT). The purpose of the study was to analyze risk factors of CMV disease in children undergoing HSCT. A total of 110 children who undergone hematopoetic stem cells transplantation were analyzed. In 16 patients (14.5%) CMV antigenemia in white blood cells was diagnosed. Most patients with CMV infection had undergone alloHSCT; one patient had undergone autologous transplantation. Second CMV reactivation in 4 of 16 patients was observed. Acute GvHD occurred in 11/15 patients. Early onset of CMV infection in 13/16 patients and late onset in 3/16 patients were diagnosed. CMV serological status of the donor and recipient before transplantation in children with CMV antigenemia was analyzed. The risk factors of CMV infection in analyzed group of children were type of transplant, recipient seropositivity before transplantation, and presence and intensity of GvHD. In most cases reactivation of CMV infection was diagnosed. CMV infection can also occur in the late post-transplantation period. CMV reactivation can occur in patients after autologous HSCT.

[Megachemotherapy followed by autologous haematopoietic stem cell rescue in children with high risk CNS tumours]. / Megachemioterapia z przeszczepieniem autologicznych hematopoetycznych komórek macierzystych u dzieci z nowotworami oun wysokiego ryzyka.

AIM: the Lublin bone marrow transplantation unit experience in megachemotherapy followed by autologus haematopoietic stem cell transplantation in children with high-risk CNS tumours is described. MATERIAL AND METHODS: 9 patients (8 boys and 1 girl) treated in our department between 1999-2004, with high risk malignant brain tumours were included into the study. Median age of the patients was 10 years (range 4-18 years). The group consisted of 5 cases of medulloblastoma, and single cases of ependynmoma, teratoma, astrocytoma anaplasticum and glioblastoma. Stem cell apheresis from peripheral blood was performed during chemotherapy after surgery. Megachemotherapy consisted of carboplatin in total dose 1200 mg/m2, etoposide in total dose 800mg/m2 and melphalan in total dose 200 mg/m2 in five patients. Remaining four children received carboplatin in total dose 1800 mg/m2, etoposide in total dose 750 mg/m and tiothepa in total dose 900 mg/m2. RESULTS: two patients relapsed one and two months after megachemotherapy respectively. No transplant related mortality was observed. Seven children are alive and well with the median observation time 23 months. CONCLUSION: megachemotherapy followed by stem cell rescue is a safe and feasible procedure in children with malignant brain tumours and may improve results of the treatment in high-risk patients, but these results should be con firmed in larger series of patients.

[Autologous stem-cell transplantations in children with non-Hodgkin lymphomas]. / Autologiczne transplantacje komórek hematopoetycznych u dzieci z chloniakami nieziarniczymi.

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.

Neurological manifestation of CMV disease after allogeneic haematopoietic stem cells transplantation--a case report.

A 4-year-old girl who underwent allo HSCT from unrelated donor and developed neurological CMV disease in early postransplant period was described. She had clinical symptoms of radiculitis confirmed with spinal MRI scans with concomitant detection of CMV in CNS by PCR. Several risk factors for CMV disease in the presented case were discussed.