bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cidofovir for Adenovirus Infection after Allogenic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 16 Childrens.
Authors: Ouachée-Chardin Marie , Leruez-Ville Marianne , Rouzioux Christine , Blanche Stéphane 
Published: October 2019

Abstract
Adenovirus is an important cause of morbidity and mortality in pediatric hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis of 16 patients treated with cidofovir as first-line therapy for adenovirus, from one center. Transplants were performed for primary immunodeficiencies (n=9), other inherited diseases (n=5), acute leukemia (n=1) and Langerhans cell histiocytosis (n=1). Six patients received HSCT from matched sibling donor, 6 from unrelated donor and 4 from a family haploidentical donor. Bone marrow was T-cell depleted in 5 transplants. Nine patients received ATG or Campath as GVHD prophylaxis. Eight patients had a acute GVHD of grade II to IV and 4 received Campath as GVH treatment. Four patients had chronic GVHD. Adenovirus subgenus were A for 10 patients, C for 5 patients and one patient had a coinfection with A and C adenovirus. Symptoms were fever (n=11), diarrhae (n=14), pneumonitis (n=4), hepatitis (n=6) and hematuria (n=1).Eight patient had a viral co-infection. Real-time quantitative PCR was used for detection and monitoring of adenovirus. The median time of first detection was day+7 after HSCT. Four patients had a first detection before HSCT and for 3 of them cidofovir was started before HSCT. All the patients had adenovirus detected from blood with a median time of day+19 afterHSCT. The median number of positive sites before HSCT was 3. Cidofovir was started at a median of 28 days after HSCT. Dosage per infusion was 5mg/kg for 8 patients and 3mg/kg for 4 patients. Four patients received 3 or 5mg/kg.A median number of four infusion was given during a median of 32 days. Median follow-up was 13 months.
Of the 16 children, 14 were successfully treated with cidofovir and two failed therapy and died from disseminated adenovirus disease. One patient died from GVHD. In total, 6 patients had no toxicity, 5 developed a reversible tubulopathy. Of note, 3 children improved under treatment suggestinfg a possible nephritis induced by adenovirus. The discontinuation of the drug was not required in any patient. We conclude that cidofovir may be efficient for adenovirus infection after HSCT in pediatric patients but prospective controlled trials are warranted.
The Disease Status at Transplant Is the Major Factor Association with the Long Term Survival of HLA Haploidentical Peripheral Blood Stem Cells Transplantation.
Authors: Wu Binyi , Wu Lanxiao , Guo Kunyuan , Song Chaoyang , Yan Dingan , Xiao Lulu 
Published: October 2019

Abstract
Objective: To evaluate the factors effecting the long term survival of refractory leukemia patients who received the therapy of HLA haploidentical peripheral blood stem cells transplantation.
Methods: To analysis the factors effecting long term survival of refractory leukemia patients who underwent HLA haploidentical peripheral blood stem cells transplantation. The HLA mismatched locus between the donors and patients, the disease status of patients at transplant, the grafted mononucleaer cells number, and the occurrence of GVHD, the age of patients and other factors were considered and analyzed by data reduction SSP11. From July, 1998 to May, 2004, 30 Patients with refractory leukemia patients including 13 cases of acute non-lymphocytes leukemia, 10 cases of acute lymphocytes leukemia, 6 cases chronic myeloid leukemia and 1 cases of non-Hodgkin lymphoma underwent HLA haploidentical peripheral blood stem cells transplantations. The median age was 25 years old (3– 52 years old). Twelve patients received stem cells from parents, four from daughter and son, and the other from sibling donors. Twelve patients received three HLA locus mismatched stem cells, thirteen patients received two HLA mismatched donors stem cells, and five patients received one HLA mismatched donors stem cells. The conditioning regime consisted of fludara (25mg/m2 X5d), busufan (4mg/kg X4d) and cyclophosphamide ( 60mg/kg X2d). Median dose of rabbit anti-human lymphocyte globulin (5mg/kg X5d) was added in the in some patients. A mean of 6.0 x 108 /kg (3–9 x108 /kg) mono-nucleated cells was grafted. The mean CD34+ cells number was 5.5 x106 /Kg (3–6.5 x106/kg).
Results: Twenty-nine patients were successfully grafted and one failed to graft. The mean time of white cell count more than 1x109/L was 13 days (10–18 days) and 12 days (9–16) respectively. Severe acute graft versus host disease occurred in six patients, and four died. Seven patients suffered from intensive chronic graft versus host disease. Nine patients relapsed and died. The mean relapse time was 10 months (3 months to 24 months). Four patients died from intensive chronic graft versus host disease. Fourteen patients are still disease free survival with high karnofsky performs. The relapse of leukemia was the main cause of death. Five the patients less than 20 year’s old age are still disease free survival with high karnofsky performs scores.
Conclusion: HLA haploidentical peripheral blood stem cells transplantation may be an effect therapy for refractory leukemia. Although graft versus leukemia effect may be strong in HLA haploidentical blood stem cells transplantation, leukemia relapse is still the main cause to death. We suggest that for these patients with leukemia who can not find full matched donor perform related HLA mismatched peripheral blood stem cells transplantation as earlier as to get the better long term outcome.
Increased Risk of Non-Relapse Mortality within One Year after Autologous Stem Cell Transplant in Older Adults with Lymphoma.
Authors: Kalaycio Matt , Pohlman Brad , Sobecks Ronald , Andresen Steven , Summers Kristie , Bolwell Brian J. , Rybicki Lisa , Kuckowski Elizabeth 
Published: October 2019

Abstract
The risk of early mortality after high-dose chemotherapy followed by autologous stem cell transplant (ASCT) is generally less than 5%. However, this mortality rate is often determined by deaths that occur while hospitalized or within 60–100 days of ASCT. We queried our long-term follow-up database to determine non-relapse mortality (NRM) for patients with lymphoma within 1 year of ASCT. From 1/1/99 to 3/30/04 we treated 317 evaluable lymphoma patients with busulfan 14mg/kg, VP-16 60 mg/kg, and cyclophosphamide 120 mg/kg followed by ASCT. Of these 317 patients, 21 (6.6%) had NRM within 1 year of ASCT. There were no significant differences between the 296 patients who did not die of NRM and the 21 who did with regard to diagnosis of non-Hodgkin versus Hodgkin lymphoma, exposure to radiation therapy, exposure to rituximab, stage, and disease status at the time of ASCT. However, the median age of the 21 patients who died of NRM was 56 years compared to 49 years in the 296 who did not (p = 0.003). Of the 21 patients who died of NRM, 13 (62%) died of pulmonary complications. Adult respiratory distress syndrome (ARDS) was listed as the cause of death (COD) in 5 patients, but nearly all patients died at other institutions limiting our ability to confirm COD. Pneumonia was the COD in 5 patients and pulmonary toxicity was the COD in 2 patients. We routinely screen patients with pulmonary function tests including DLCO before and approximately 42 days after ASCT. There was no significant decrease in the median pre-ASCT and the post-ASCT DLCO in either the whole cohort of patients dying of NRM or the 13 patients dying of pulmonary complications. The 8 patients with NRM, but not pulmonary complications, died of various causes including cardiac tamponade, sepsis/multi-system organ failure, cirrhosis, renal failure, and secondary malignancy. The median time from ASCT to NRM was 146 days (range 45 to 287 days). Thus, lymphoma patients remain at risk for NRM for several months after ASCT. Older patients are at particular risk. The most common COD is pulmonary failure that cannot be predicted by screening pulmonary function tests. The cause of the pulmonary failure is uncertain. Busulfan may cause pulmonary toxicity, but the dose in this series of patients is relatively low and we have not seen similar pulmonary complications in 95 patients (median age 52 years) with myeloma treated with the combination of busulfan 16 mg/kg and cyclophosphamide 120mg/kg.
The Application of Sequential and Quantitative Analysis of Donor Chimerism in Adoptive Immunotherapy Following Allogeneic Stem Cell Transplantation.
Authors: Tang Xiaowen , Wu De Pei , Sun Aining , Zhu Ziling , Chang Huirong , Ruan Changgeng 
Published: October 2019

Abstract
Objective In order to investigate the value of sequential and quantitative analysis of chimerism to predict relapse or graft rejection after allogeneic stem cell transplantation, to determine the optional time point of adoptive immunotherapy and to estimate the efficacy of adoptive immunotherapy.
Methods 70 patients who received HLA compatible allo-HSCT were evaluated. Peripheral blood and bone marrow were collected before and after transplantation in different period. Serial and quantitative analysis of donor chimerism (DC) both prior to and following adoptive immunotherapy were performed by multiplex PCR amplification of STR markers (STR-PCR) and capillary electrophoresis with fluorescence detection.
Results 13 of 70 patients relapsed at median time of 6months post transplant (4/13 patients developed hematologic relapse and 9/13 patients appeared cytogenetic or molecular relapse respectively). 2 of 70 patients experienced graft rejection. Before the time of relapse or graft rejection, STR-PCR indicated the decreasing DC in all 15 patients, at levels ranging from 24.8%~86.2%. The declining value of donor chimerism (DC< 90%) was detected in four patients 26 days before relapse or graft rejection diagnosed clinically. Adoptive immunotherapy was used to treat 15 patients(9 CML, 5 AML, 1 MDS). A response to immunotherapy was achieved in 6 patients(6 CML) following withdrawal of CsA and in a further 4 patients(2 CML, 1 M2, 1 MDS) after additional donor lymphocyte infusion(DLI). In these patients, the value of DC increased with convertion to a predominant donor profile (>90%) or converted to stable full donor chimerism(FDC)(6 patients) or stable mixed chimerism(MC)(4 patients) shortly after immunotherapy. All these 10 patients who responsed to immunotherapy developed acute or chronic GVHD. While in the patients without response, the level of DC decreased persistently or declined after transient increasing. Three patients without response received second DLI but remain failed to therapy.
Conclution The results demonstrate that the decreasing value of DC can identify the patients who have high risk of relapse or graft failure and can be used to guide adoptive immunotherapy implementation at early stage. The sequential and quantitative monitoring of DC has been shown to be a valuable tool to determine the optional time point of immunotherapy and to early evaluate the efficacy of treatment. Furthermore, it can present a rational basis for treatment intensification in patients who did not respond to first-line DLI treatment
Reduced Intensity Conditioning Regimen for Allografting Following Cytoreductive Autografting in Relapsed/Resistant Hodgkin’s Lymphoma.
Authors: Carella Michele , Beltrami Germana , Corsetti Maria T. , Greco Mario M. , Scalzulli Potito , Cascavilla Nicola , Musto Pellegrino , La Sala Antonio , Dell’Olio Matteo , Carella A.M. 
Published: October 2019

Abstract
Background: We postulated that it is possibile to safely extend the benefit of allografting to relapsed or resistant Hodgkin’s Lymphoma (HL) by combining cytoreduction with high-dose therapy/autologous stem cell transplant (HDT/ASCT) and graft versus HL effect mediated through transplanted donor immune cells with nonmyeloablative allografting (RICT).
Methods: Twenty-two patients, 32 years of age (range, 16–39) with heavily pretreated disease were given HDT/ASCT. At a median of 92 days after HDT/ASCT the patients received fludarabine 30 mg/m2/day x 3 days and cyclophosphamide 300 mg/m2/day x 3 days and non-T depleted donor peripheral blood stem cells from HLA-identical siblings. Postgrafting immunosuppression consisted of methotrexate and cyclosporine. Cyclosporine was withdrawn early in patients with mixed chimerism or disease progression. Donor lymphocyte infusions were given to 12 patients with stable mixed chimerism and/or progressive disease.
Results: Seventeen patients (77%) achieved full chimerism and 5 patients mixed chimerism. Twelve patients (55%) achieved CR after tandem transplant. The first signs of responsiveness in CR patients began at day ≥60 and the maximal response was achieved on day ≥80. The remitters patients achieved full chimerism and developed acute/chronic GVHD before regression of the disease; moreover, 5 patients achieved CR after DLI. At last follow-up (July 31, 2004), 9 out of 12 CR patients are alive at a median of 1844 days (range, 1092 to 2045). Subsequently, 5 patients relapsed and are now alive on therapy and four patients maintain CR after a median follow-up of 1874 days (range, 1092–2045). Acute GVHD grade ≥ II occurred in 9 patients (40%); chronic GVHD developed in 5 patients (23%), four of them with extensive chronic GVHD requiring further immunosuppressive therapy. Two patients died of GVHD/infections, 1 patient died of extensive chronic GVHD and 7 patients of progressive disease.
Conclusions: This tandem auto-allotransplant protocol demonstrated to be highly effective also in advanced resistant Hodgkin’s Lymphoma patients. The exploitation of graft-versus-lymphoma effect is a promising finding
Fludarabine and Busulfan (FluBuP Regimen) as Myeloablative Conditioning Regimen for Allogeneic PBSCT in 71 Leukemic Patients (A Unicenteric Study).
Authors: Iravani Masoud , Tavakoli Maryam , Shamshiri Ahmad Reza , Evazi Mohammad Reza , Mousavi Asadollah , Bahar Babak , Ghavamzadeh Ardeshir 
Published: October 2019

Abstract
Following 3 other centers in USA, Canada and Germany, we are evaluating fludarabine (40 mg/m2 on days −6 to −2) and busulfan (4 mg/kg/day on days −5 to −2) as a new conditioning regimen for allogeneic peripheral blood stem cell transplantation in leukemic patients with matched related donors. Seventy one patients were enrolled, 18 with high and 53 with standard risk (18 ALL, 35 AML, 16 CML and 2 MDS; F=29 M=42). The median patient age was 23.7 years(range, 2.4– 46.7). Cyclosporine was used as a prophylactic agent for GVHD (3mg/kg IV till +4, 10 mg/kg oral from day +5). The median follow-up was 269 days (range, 50–459 days). 91.5% and 15.5% developed mucositis and hepatic toxicity respectively which resolved with conservative therapy. There was no cardiac toxicity (except one patient with mild pericardial effusion and another with tachycardia). The median of highest serum creatinin level during hospitalization were 1.6 mg/dl (range, 0.8–3.7; 24.3% with Cr>2) and serum cyclosporine level, at the same time, was 246 ng/ml (range, 9–814). 7% experienced hemorrhagic cystitis (infection was ruled out) and 36.6% experienced moderate to severe headache. 38% and 14.1% of the patients showed grade 1, 2 and grade 3 acute GVHD respectively. Grade 4 acute GVHD was found in one patient. 50% and 6% showed limited and extensive chronic GVHD. 27% of patients became CMV+ (min +17, max +69). The median time for neutrophil and platelet recovery were 10 (min 0, max +26) and 12 (min 0, max +30) days. In day +38, 86.7% of the patients had 90% or more, mononuclear chimerism (with STR-PCR technique; median, 97%; range, 25–100). 5 ALL and 8 AML patients relapsed (18.3% of all patients) and 6 (8.45%) died after relapse. Nonrelapse mortality was 13% (9 patients; acute GVHD grade IV=1, CMV infection and GVHD=2, CMV infection=2, pneumonia=2, infection=2). With a median follow up of 9 months (range, 1.6–15.3 months), the probability of overall survival and disease free survival were 79.68% and 81.26% respectively. It could be beneficial to use fludarabine versus cyclophosphamide in standard conditioning regimen for leukemic patients because of reduced toxicity, low incidence of acute GVHD and facilitated donor engraftment.
Purified T Depleted Peripheral Blood and Bone Marrow CD34 Transplantation from Haploidentical Mother to Child with Thalassemia.
Authors: Sodani Pietro , Andreani Marco , Polchi Paola , Gaziev Javid , Centis Filippo , Giardini Claudio , Nesci Sonia , Cicconi Silvia , Spitaleri Luca , Cassiani Flaminia , Lucarelli Guido 
Published: October 2019

Abstract
Approximately 60% of thalassemic patients can not apply to “gene terapy today” which the insertion of one allogenic HLA identical stem cell into the empty bone marrow as the vector of the normal gene for beta globin chain synthesis. We studied the use of the haploidentical mother as the donor of hematopoietic stem cells assuming that the immuno-tollerance estabilished during the pregnancy will help to bypass the HLA disparity and allow the hemopoietic allogeneic reconstitution in the thalassemic recipient of the transplant.We have employed a new preparative regimen for the transplant in nine thalassemic children aged 3 to 8 years ( median age 5 years ) using T cell depleted peripheral blood stem cell (PBSCTs) plus bone marrow (BM) stem cells.. All patients received hydroxyurea (OHU) 60 mg/kg and azathioprine 3 mg/kg from day −59 untill day−11, fludarabine (FLU) 30 mg/m 2 from day −17 to day −11, busulphan (BU) 14 mg/kg starting on day −10, and cyclophosphamide(CY) 200mg/kg, Thiotepa 10 mg/kg and ATG Sangstat 2.5 mg/kg, followed by a CD34 + t cell depleted (CliniMacs sistem), granulocyte colony stimulating factor (G-csf) mobilized PBSC from their HLA haploidentical mother. The purity of CD34+ cells after MACS sorting was 98–99%, the average number of transplanted CD34+ cells was 15, 4 x 10 6/kg and the average number of infused T lymphocytes from BM was 1,8 x 10 5/Kg.The patients received cyclosporin after transplant for graft versus host disease( GVHD) prophilaxis. Four patients rejected the transplant and are alive with thalassemia: one patient received a different dose of CD3 without cyclosporine after transplant, two patients received a lower dose of CD34+, in the fourth patient the donor has been the haploidentical father instead than the mother. One of the nine patients, after the failure of the transplant from the mother, received a second transplant using purified CD34+ cells from the father, using the same preparative regimen and achieved a complete hematopoietic reconstitution. Six patients are alive disease free with a median follow up of 19 months (range 7–30). None of the six patients showed AGVHR. This preliminary study suggest that the transplantation of megadose of haploidentical CD34+ cell from the mother is a realistic therapeutic option for those thalassemic patients whithout genotipically or phenotipically HLA identical donor.
Stem Cell Transplantation from Mismatched Related Donors for Paediatric Haematological Disorders : The Hospital for Sick Children, Toronto, Experience.
Authors: Nicolin Gary , Das Prabodh , McDougall Elizabeth , Gassas Adam , Sung Lillian , Lau Wendy , Saunders E. Fred , Doyle John , Calderwood Stan 
Published: October 2019

Abstract
Between June 1994 and December 2003, 31 patients with haematological disorders presenting at the Hospital for Sick Children, Toronto, Canada, received a stem cell transplant (SCT) from a mismatched related donor. Diagnoses included ALL (15), AML (10), CML (1), JMML (1), SAA (2), de novo MDS (1) and Fanconi anaemia (1). Patients were aged between 0.9 to 17.8 years (mean 8.5 years). There were 20 males and 11 females. HLA typing included A, B and DRB1 on all patients (Class 1 alleles by low resolution molecular technique and Class 2 by high resolution technique). 22 patients had 1 major mismatch and 9 had 2–3 major mismatches. The source of stem cells was bone marrow in 15 patients (mean total nucleated cell dose 4.44 x 108/kg, range 1.89–6.63), peripheral blood (PBSC) in 15 patients (mean CD34 dose 11.80 x 106/kg, range 3.19–42.18) and one patient received both BM and PBSC. Of those who received PBSC, 9 had CD34 selection, 3 had CD34 selection and T-cell depletion, and 3 received an unmodified product. Conditioning regimens included cyclophosphamide and total body irradiation (TBI) (15), etoposide and TBI (6), busulfan and cyclophosphamide (6), etoposide and cyclophosphamide (1), fludarabine, cyclophosphamide and TBI (1), fludarabine and cyclophosphamide (1) and fludarabine, melphalan and thiotepa (1). Graft versus host disease (GvHD) prophylaxis included combinations of cyclosporine A, methotrexate, anti-thymocyte globulin and methylprednisolone. There was one primary graft failure and 3 secondary graft failures. Mean time to neutrophil engraftment was 17 days (range 9–36). The incidence of acute and chronic GvHD was 48% and 51% respectively. Of the 31 patients, 15 are alive (12 in complete remission (one of these with a secondary brain tumour) and 3 with relapsed disease) and 16 are dead (3 of relapsed progressive disease, 12 from transplant related mortality (TRM - 9 of these were in CR) and in one the cause is not known). Three year actuarial OS and EFS for the entire group were 50±9% and 45±9%, OS and EFS for those matched at 5/6 loci were 56±11% and 44±11% and OS and EFS for 3/6 and 4/6 matched were 38±16% and 36±16%. The mean follow-up time for survivors is 5.6 years (range 11.6 months to 9.7 years). In this series, there was no significant difference in survival when comparing BM vs. PBSC harvests; in one vs. 2–3 mismatch donors; and in the presence vs. absence of acute or chronic GvHD. These results confirm the feasibility and efficacy of using mismatched related donors for paediatric haematological disorders. Steps should be taken to decrease the TRM to achieve a better survival rate.