bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytomegalovirus Viraemia after Allogeneic Transplant: A Prospective Study of a Risk-Adapted Strategy in a Single Transplant Unit.
Authors: Johnston Amanda J. , Dodds Anthony J. , Ma David D. , Milliken Samuel T. , Fay Keith C. , Cunningham Philip H. , Moore John J. 
Published: April 2020

Abstract
CMV infection causes significant morbidity and mortality following allogeneic transplantation. In 2003, the NSW Bone Marrow Transplant network adopted a uniform CMV prevention policy. This prospective study aimed to evaluate the impact of the policy on the rate, management and outcome of CMV reactivation in allogeneic transplant recipients at St Vincent’s Hospital, Sydney. All patients at high risk for CMV reactivation (recipient and/or donor CMV seropositive pre-transplant) had weekly blood samples screened using nucleic acid tests for CMV RNA and DNA. Patients with a related donor were screened from day +21 to +84 post-transplant and received antiviral treatment for CMV only if reactivation was detected. Patients with an unrelated donor received ganciclovir 5mg/kg 3x/week from day +21 to +84, in addition to screening tests. Between October 2003 and June 2005, 40 patients (median age 44 years, range 20-67) received allogeneic transplants, with 21 (53%) originating from an unrelated donor. Thirty-six (90%) patients were high risk for CMV disease and 13 (33%) developed CMV viraemia at a median of 39 days (range 16–101) post-transplant. Six of the 13 (46%) PCR positive patients had unrelated donors, and three had severe, steroid resistant GVHD requiring monoclonal antibody therapy. The median CMV viral load was 3200 copies/mL (range 870 to &gt;100,000) and three of the 13 patients had CMV disease (all biopsy-proven CMV enteritis). All viraemic patients were treated with ganciclovir 5mg/kg BD for a median of 2 weeks, with clinical improvement and reduction in viral load in 10 patients. Overall survival of the CMV viraemia group was 85% at a median of 303 days follow up, compared with 78% for the whole group (p = NS). The described risk-adapted CMV preventive strategy is associated with acceptable rates of viral reactivation and low morbidity and mortality post-allogeneic transplant.
Eosinophilia, Positive ANA, and Hypergammaglobulinemia at Presentation of Extensive Chronic GVHD in Children: A Children’s Oncology Group Study.
Authors: Jacobsohn David A. , Schultz Kirk R. , Goldman Frederick , Wall Donna A. , Krailo Mark , Chen Zhengjia , Lipton Jeffrey M. , Sanders Jean E. , Gilman Andrew L. 
Published: April 2020

Abstract
Because of the variable and often protean manifestations of chronic GVHD, its diagnosis is difficult and based solely on clinical features. As part of a Children’s Oncology Group multi-institutional clinical trial (ASCT0031 - a randomized study of hydroxychloroquine plus standard therapy for children with newly-diagnosed extensive chronic GVHD), we prospectively evaluated laboratory markers that have been previously reported in single-institution studies to be associated with chronic GVHD. Fifty-four patients were enrolled: median age 12 (1–21) yrs: 37M/17F. The diagnosis of extensive chronic GVHD was made at a median of 210 days (range 82–914) following transplant. Eighteen of 45(40%) patients had eosinophilia (absolute eosinophil count (AEC)≥500/μL). Twelve of 43 (28%) patients had an anti-nuclear antibody (ANA) titer ≥1:80 and 9 of these (21%) had a titer ≥1:160. Finally, 11 of 48 (23%) patients had an elevated IgG level. At presentation, 67% of patients had one or more of eosinophilia, ANA≥1:80, and hyper-IgG. A Th-2 predominance is suggested by eosinophilia (↑ IL-5) and hyper-IgG and positive ANA (↑ IL-4). Of note, of 9 patients with sclerodermatous chronic GVHD, 6 had hyper-IgG and 5 had eosinophilia. These results support a Th2 predominance in a major subset of children presenting with chronic GVHD. These results emphasize the importance of including evaluation of eosinophil count, ANA, and IgG level as tests supportive of the diagnosis of chronic GVHD in children.
Immunological, Molecular and Cytokine Changes after Reduced Intensity Bone Marrow Transplantation for PNH: A 2 Years Follow-Up.
Authors: Barcellini Wilma , Imperiali Francesca G. , Zaninoni Anna , Fermo Elisa , Boschetti Carla , Soligo Davide , Deliliers Giorgio Lambertenghi , Zanella Alberto 
Published: April 2020

Abstract
We describe the clinical, immunological and molecular characteristics of a 39 yrs-old male with 8 yrs story of paroxysmal nocturnal hemoglobinuria (PNH) who underwent a reduced intensity conditioning bone marrow transplantation (RIC-BMT) from identical sibling donor. The patient was pancytopenic, transfusion-dependent and had suffered from Budd-Chiari syndrome. We already reported that that RIC-BMT restored clonogenic erythroid activity and cytokine production (IL-2, IFN-gamma and TNF-alpha) in BM. Likewise, IL-2, TNF-alpha and TGF-beta formerly increased in both BM and peripheral blood (PB), became normal after BMT. Finally, the PNH clone was no more detectable in both BM and PB cells by molecular analysis 1 year after RIC-BMT. At 2 years after the transplant the patient is well, with Hb levels of 15.2 g/dL, but with low WBC (2.7x109/L) and platelets (71x109/L). The number of CFU-GM and BFU-E in BM further increased and none of the CFU-GM and BFU-E showed the original PIG-A gene mutation. Likewise, none of the PB granulocytes showed the original PIG-A gene mutation also 2 years after BMT. These immunological, molecular and cytokine changes observed 2 years after RIC-BMT support the curative action of a donor immune-mediated “graft versus PNH” effect.
Patient before BMT 1mo after BMT 6mo after BMT 12mo after BMT 24mo after BMT Controls (mean±SE) CFU-GM 7 10 7 10 13 21±9 BFU-E 12 23 46 108 115 62±18
Graft Versus Leukemia (GVL) Effect in the Central Nervous System Sanctuary: Successful Treatment with Donor Lymphocyte Infusion (DLI) in a Patient with Resistant Ph1+ Acute Lymphoblastic Leukemia.
Authors: Ostronoff Mauricio , Domingues Mariana Coutinho , Ostronoff Fabiana , Calixto Rodolfo , Souto Ana Patricia , Sucupira Alexandre , Florêncio Rodrigo , Matias Kleber , Tagliari Clemente 
Published: April 2020

Abstract
Ph1+ ALL requires allo- BMT in first CR, however disease relapse continues to be a concern. We report a patient with refractory ALL Ph+1 treated with conventional allo-BMT who had an isolated CNS relapse 2 years later successfully rescued with chemotherapy followed by DLI. In September 2002 a 35-year-old male patient presented with deep venous thrombosis of the right popliteal vein. The WBC was 84X109 / l (52% blasts). Bone marrow: ALL Ph1+, bcr/abl, pre-B CALLA+. CSF: normal. Induction chemotherapy according to LAL-adult French protocol included idarubicin, vincristine, cytoxan, corticosteroids and MADIT weekly. CR obtained D+28. CHOP + MADIT were then administered. In the next 2 weeks he had a marrow relapse (39% blasts) just before start allo-BMT conditioning and we decided together to go on: FTBI (12 Gy-6 fractions) + CTX 120mg/kg, GVHD prophylaxis with CSA alone and infusion of 3,5 X 106 CD34/kg of peripheral stem cell from his HLA identical brother. Chronic extensive GVHD was observed 6 months later treated with a short course of corticosteroids. 2 years after BMT pt presented severe radicular pain and weakness in his right leg. Bone marrow showed persistent cytologic, cytogenetic and molecular CR. VNTR 100% donor. CSF was infiltrated with blasts (bcr / abl +) and MRI showed a paravertebral tumor at L4 level. 4 cycles of salvage chemotherapy with high dose methotrexate (3g/m2) and ara-C (2g/m2 x 2 x 3 days) + MADIT obtained clinical and CSF CR. DLI from the same donor was performed twice at 1 month interval without GVHD. One year has elapsed since then and he is in continuous CR. We conclude that DLI might induce a GVL effect on CNS acute leukemia and therefore DLI should be helpful in achieving higher donor immunoreactivity and a better GVL effect.
Lymphocyte counts in first and second DLI DLI I total 1,3x108 CD8 0,4x108 CD3 0,97x108 DLI II total 0,6x108 CD8 0,21x108 CD3 0,47x108
Clinical Relevance of CRp in Untreated AML.
Authors: Estey Elihu H. , Garcia-Manero Guillermo , Giles Francis J. , Cortes Jorge , O’Brien Susan , Kantarjian Hagop M. 
Published: April 2020

Abstract
For many years response to induction therapy for AML was classified as CR or no CR. Recently, responses less than CR, e.g. CR with incomplete platelet recovery (CRp), have also been recognized. Attaining CRp suggests that a treatment is more “active” than if neither CR nor CRp had occurred (“resistant”). However, the question of whether CRp conveys clinical benefit has received relatively little attention; in particular, what is the effect of CRp on subsequent survival probability (“SSP”) relative to CR or resistant? The database we used to address this question consisted of 1051 consecutive pts with untreated AML (APL excepted) or high-risk MDS (&gt; 10% blasts) considered for induction therapy at MDA from 2000 through 2004. 5% of the pts declined therapy, 45% achieved CR and 5% CRp, as usually defined, while 29% were resistant, i.e. they survived at least 1 month after beginning therapy, without ever achieving CR or CRp, or showed obvious reappearance of blasts before the end of this month; the remaining pts were called “early deaths” and were not further considered. CRp rates were higher among pts with abnormalities of chromosomes 5 and/or 7 (−5/−7; 15% CRp in 264 pts) than among other cytogenetic subsets (CRp rate 4–6%), with the following number of CRps for every 100 CRs: −5/−7 53.6, inv (16) or t(8;21) 5.5, normal karyotype 7.5, other cytogenetic abnormalities 15.4.The median number of days to CR was 31, CRp 44, and resistant 40, while the 75th percentiles were 38, 60, and 59 respectively. Although many induction regimens were used, we, for simplicity, classified these as either “higher” or “lower” intensity, with the former (HI, 914 pts) corresponding to “chemotherapy” and the latter (LI) to “targeted therapy”, as commonly accepted. CR and CRp rates were 51% and 5% for HI and 5% and &lt; 1% for LI. In general, pts continued to receive their initial induction regimen regardless of whether their reponse was considered CR or CRp. Because 75% of pts who eventually achieved CRp did so within 60 days of starting induction therapy, as did 90% of the CR pts, we categorized pts alive on day 60 according to whether they ultimately achieved CR, CRp, or neither (resistant). We then dated SSP from day 60:
Figure Figure
Sensitivity analyses dating SSP from day 30 or day 90, rather than day 60, produced similar results. We are: (1) doing a multivariate analysis examining the relative effects on SSP of response, cytogenetics (given the association of poor prognosis cytogenetics with CRp), and treatment after relapse, and (2) assessing whether the effects of CR vs CRp vary according to induction treatment. Our current results, however, constitute the first demonstration that CRp is of clinical relevance in untreated AML.
Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Secondary Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndromes (MDS).
Authors: El-Cheikh Jean , Faucher Catherine , Mohty Mohamad , Stoppa Anne-Marie , Lafage-Pochitaloff Marina , Coso Diane , Moziconacci Marie-Joelle , Bouabdallah Reda , Gastaut Jean-Albert , Blaise Didier , Vey Norbert 
Published: April 2020

Abstract
Secondary AML and high risk MDS represent a poor risk group of myeloid malignancies. We report here the results of a single center retrospective study of allo-SCT in 28 patients (median age, 42 y.) with secondary AML (n=19; 68%) and MDS (n=9; 22%). Eleven patients (39%) had therapy-related AML (t-AML). FAB categories included: AR/ARS: 3, AREB/AREBt: 6, M0: 1, M1–M2: 9, M4–M5: 5, M6: 3, and one patient could not be classified. Cytogenetics features were: poor risk in 20 patients (71%), normal in 5 patients (19%) and not evaluated in 3 (10%). Allo-SCT was performed as first line therapy in 9 patients (32%) of whom 7 MDS and 2 sAML. The remaining 19 patients (68%), were transplanted after initial induction chemotherapy of whom 17 sAML (89%), and 2 MDS (11%). Median interval between diagnosis and allo-SCT was 3.6 months (range, 1–12). 12 patients (43%) were in complete remission at time of allo-SCT, while 9 patients (32%) were refractory or in progression after treatment, and 7 patients (25%) had stable disease. In 25 cases (89%) donor was a HLA identical sibling, and in 3 cases (11%) a matched unrelated donor. The conditioning regimen was fully myeloablative in 19 patients (68%) including Cy-TBI or BU-Mel or a reduced intensity conditioning (RIC) in 9 patients (32%). Nineteen patients (68%) died after transplantation, of whom 12 patients from non relapse causes (GVHD: 5; infections: 6; multi-organ failure: 1). Seven patients (25%) died from relapse or progression of the disease including 5 patients (18%) with AML and 2 patients (7%) with MDS. The one-year cumulative incidence of transplant related mortality (TRM) was 38%, with TRM being significantly lower in the RIC allo-SCT group (13% vs. 43%; P=0.06). With a median follow-up of 30 months, the probability of progression after transplantation at 5 years was 51% (95%CI, 39–73). Five-year overall survival (OS) was 26% (95%CI, 13–48). Most importantly, none of the pre-transplant parameters influenced OS or DFS. In all, these results suggest that standard allo-SCT is associated with a high TRM rate not allowing a breakthrough in the outcome of patients with secondary AML and high-risk MDS. The use of a RIC regimen significantly decreased TRM in this high risk group of patients, likely representing an attractive modality to develop novel strategies and further refine the allogeneic anti-leukemic activity for a better outcome.
Effective Treatment with Imatinib Mesylate and Donor Lymphocyte Infusion Following Relapse after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myeloid Leukemia.
Authors: Li Jianyong , Wu Hanxin , Qian Sixuan , Hong Ming , Xiao Bing , Zhang Run , Ruan Changgeng 
Published: April 2020

Abstract
Imatinib mesylate (STI571) and donor lymphocyte infusion (DLI) were two most effective treatment for chronic myeloid leukemia (CML) relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the combination of STI571 and DLI was rarely reported in the treatment of CML relapse after allo-HSCT. To explore the effect of STI571 with DLI in the treatment of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for CML, two relapsed CML patients after allo-HSCT were treated with short course (&lt;1 month) of STI571 400 mg or 600 mg/d and DLI. Case 1, female, 32 years old (yrs), transformed to acute myeloid leukemia (AML) M2 four months after diagnosis of CML. The patient did not response to STI571 600 mg/d for two months and received HLA haploidentical brother bone marrow transplantation (BMT) without ex-vivo T cell depletion and acquired complete remission (CR). 100 days after transplantation, the patient relapsed in the form of AML-M2. Case 2, female, 54 yrs, five months after diagnosis of CML, she received HLA-identical brother HSCT and acquired CR. Four months after transplantation, karyotyping showed 46, XX, t(9;22)(q34;q11)[7]/46, idem, +mar1, +mar2,+mar3[3], FISH showed 500/1000 donor cells, which suggested disease progression. 31 days (case 1) and 26 days (case 2) respectively after treatment with STI571 and DLI, they acquired CR which was confirmed by morphology, normal karyotype by conventional cytogenetics and X/Y, BCR/ABL FISH, and negative BCR/ABL by FISH and RT-PCR. As of July 2005, the two patients were in continuous complete remission for 25 (case 1) and 24 (case 2) months. We conclude that Imatinib mesylate with DLI is very effective in the treatment CML after relapse following allo-HSCT, and deserve further investigation for its effectiveness and mechanism.
Reduced-Intensity Allogeneic Stem Cell Transplantation for Relapsed/Refractory Hodgkin and Non-Hodgkin Lymphoma.
Authors: Lerner Decio , Azevedo Alexandre M. , Colares Marta , Tavares Rita de Cássia B. , Maradei Simone C. , Lima Joana , Lobo Ana Maria G. , Tabak Daniel G. , Urago Katia , Lima Maria Claudia , Maiolino Angelo , Bouzas Luis Fernando S. 
Published: April 2020

Abstract
There are few treatment options for pts with multiply relapsed or refractory lymphoma. Allogeneic stem cell transplantation has historically been limited in this group by high transplant-related mortality (TRM) rates, and evidence for a clinically relevant graft-versus-lymphoma (GvL) effect has been limited. We evaluated reduced-intensity transplantation (RIT) in these pts with the aim of reducing TRM while exploiting the GvL effect. Between 12/00 and 02/05, 31 pts with an HLA-identical sibling were enrolled, 18 with non-Hodgkin (NHL) and 13 with Hodgkin (HL) lymphoma. Main characteristics were: median age = 33 years (range, 17–60); male gender = 20; histology = diffuse large B cell (9), T-cell anaplastic large cell (2), transformed-large cell (2), mantle cell, lymphoplasmacytic, T-peripheral, diffuse mixed large and small cell (1 each), and Hodgkin lymphoma (13). At study entry, 19 pts (36% NHL, 92% HL) had previously failed autologous transplantation (AT) and even patients who had not received high-dose chemotherapy had failed a median of 4+ lines of therapy. Five patients were in partial remission, 2 in untreated relapse post-AT and 24 had chemorefractory disease. Conditioning consisted of fludarabine (25 mg/m2 x 5 d) and cyclophosphamide (60 mg/kg x 2 d). Twenty nine pts received peripheral blood and 2 received marrow stem cells. GVHD prophylaxis comprised cyclosporin and mini-methotrexate. Early death occurred in 3 pts from aspergillosis, pulmonary fibrosis and cardiac failure. All other patients engrafted, 1 with a progressively autologous pattern of chimerism. The overall incidende of grades II, III and IV acute GVHD was 50%, 10% and 7%, respectively. Chronic extensive GVHD occurred in 7/23 (30%) of evaluable pts. Eight pts (25%) died of progressive disease and 9 (29%) of non-relapse causes at a median of 2.5 (range, 1–12) months. Median overall and disease-free survival for all pts is 15.3 months and 7.9 months, respectively. Differences in overall and disease-free survival were not statistically significant between pts with NHL and HL (15.3 vs 25.2 months, p = 0.7; 5.9 vs 8.1, p = 0.44; respectively). Seven pts remain alive and disease-free (HL = 2/13 [15%]; NHL = 5/18 [27%]; p = 0.66) at median follow-up of 33.7 (range, 13.2 – 54.5) months. Allogeneic RIT is a reasonable therapeutic alternative for pts with relapsed NHL or HL, even those who have relapsed after AT. Mortality rates were acceptable for this heavily pretreated group of patients.
Reduced-Intenisty Unrelated Cord Blood Transplantation for Patients with Advanced Malignant Lymphoma.
Authors: Uchida Naoyuki , Miyakoshi Shigesaburo , Matsumura Tomoko , Yuji Koichiro , Takagi Shinsuke , Kato Daisuke , Kawano Tomomi , Kusumi Eiji , Masuoka Kazuhiro , Wake Atsushi , Taniguchi Shuichi 
Published: April 2020

Abstract
Allogeneic stem cell transplantation has been potentially curative approach for advanced malignant lymphoma. Unrelated umbilical cord blood cell has become a viable source of transplantation for those who lack suitable donors, but the outcome of the transplantation with reduced-intensity conditioning has not been clearly defined yet. We have therefore analysed the outcome of the patients with advanced malignant lymphoma who have undergone reduced-intensity unrelated cord blood transplantation (RI-UCBT). Thirty patients (median age, 47 years; range 27–69 years) underwent RI-UCBT with a preparative regimen consisting mainly of fludarabine 125 mg/m2, melphalan 80 mg/m2, and 4 Gy of total body irradiation since June 2002 to June 2005 with a mean follow-up of 353 days (59–621 days). The types of lymphoma included in this study were DLBCL (11 cases), PTCL (5), Hodgkin disease (5), Follicular lymphoma (5), AITL (2), ALCL (1), and nasal NK/T lymphoma (1). All the patients were heavily treated before proceeding to RI-UCBT, including 9 with prior autologous and 1 allogeneic transplantation. The median infused total cell dose was 2.71 x 107/kg (range, 1.76–4.76 x 107/kg). Graft-versus host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Twenty-four patients (80%) achieved primary neutrophil engraftment at a median of 23 days (12–33 days), and 18 (60%) achieved platelet engraftment at a median of 40 days (26–77 days). Fourteen patients (57.1%) developed grade II to IV acute GVHD at a median of 31 days (15–59 days). Five patients subsequently relapsed and all died within 2 years. Fifteen patients died of non-relapse causes such as infection (8), GVHD (3), IP (2), and others (2). Transplant-related mortality (TRM) within 100 days was 54%. The estimated 1-year probability of overall survival was 24% (95%CI: 1–46%). In subgroup analyses, standard risk patients (CR1, CR2, PR1, n=5) showed 80% while high risk (n=25) showed 13% overall survival at 1 year. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack HLA-matched donors. Although the patients in standard risk can expect reasonably good overall survival, the beneficial effect is only limited to small part of the high risk patients. To further improve the outcome, RI-UCBT should be investigated among patients with less advanced diseases in a well-designed clinical trial.
Figure Figure
Reactivation of Cytomegalovirus Following Reduced-Intensity Cord Blood Transplantation for Adult Patients.
Authors: Matsumura Tomoko , Kami Masahiro , Kusumi Eiji , Myojo Tomohiro , Takagi Shinsuke , Kato Daisuke , Yuji Koichiro , Uchida Naoyuki , Masuoka Kazuhiro , Wake Atsushi , Miyakoshi Shigesaburo , Morinaga Shinichi , Kanda Yoshinobu , Taniguchi Shuichi 
Published: April 2020

Abstract
Backgrounds: Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem-cell transplantation. We and other groups recently reported the feasibility of cord blood transplantation using reduced-intensity regimens (RI-CBT) for adult patients with advanced hematologic diseases. We have little information on the clinical features of CMV reactivation after RI-CBT.
Patients/methods: We reviewed medical records of 142 patients who received RI-CBT at Toranomon Hospital between January 2002 and March 2005. Median age of the patients was 55 years (range 17–79). Underlying diseases were chemorefractory hematologic diseases (n=136) and severe aplastic anemia (n=6). Conditioning regimens comprised fludarabine 125 mg/m2, melphalan 80 mg/m2 and total body irradiation (TBI) (4–8 Gy). Graft-versus-host disease (GVHD) prophylaxis was cyclosporine (n=86) or tacrolimus (n=56). Median number of total nucleated cells and CD34+ cells was 2.7×106 cells/kg (0.39–4.8), and 0.73×105 cells/kg (0.03–5.7) respectively. HLA disparity was 6/6 (n=3), 5/6 (n=21), 4/6 (n=116), and 3/6 (n=2). All the patients were monitored CMV-antigenemia weekly and received pre-emptive ganciclovir or foscarnet.
Results: CMV antigenemia tested positive in 77 patients on a median of day 36 (range, 4–87) after RI-CBT. Median of maximal CMV antigenemia was 22 per 50,000 leukocytes (range, 1–1806). CMV diseases developed in 18 patients on a median of day 40 (range 15–99); enterocolitis (n=18), and adrenalitis (n=1). CMV-antigenemia remained negative in two patients, when CMV disease was diagnosed. CMV disease was successfully treated using ganciclovir or foscarnet in 17 patients, and the other patient died of septic shock. Multivariate analysis revealed grade II–IV acute GVHD as a risk factor (odds, 95% CI).
Discussion: CMV reactivation and diseases develop early after RI-CBT. Optimal strategy for preventing CMV disease should be established in RICBT.