bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic Stem Cell Transplantation in Idiopathic Myelofibrosis: The Italian Experience.
Authors: Patriarca Francesca F. , Sperotto Alessandra A. , Bruno Barbara B. , Bacigalupo Andrea A. , Bosi Alberto A. , Fanin Renato R. 
Published: October 2019

Abstract
Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative treatment for idiopathic myelofibrosis (IM), but it is associated with a high transplantation-related (TRM) mortality rate, especially in advanced and elderly patients. Recently, reduced-intensity conditioning (RIC) regimens were reported to be feasible in these subgroups of patients. Herein, we reported a preliminary analysis of the data of the Gruppo Italiano Trapianto Midollo Osseo (G.I.T.M.O.) Registry regarding a total of 92 patients with IM, who underwent allogeneic HSCT in 25 different Italian Transplant Centres between 1986 and 2005. One Centre performed 26 transplants, 4 Institutions performed between 6 and 10 transplants and the other 20 Centres realized five or less procedures. Ten transplants (11 %) were performed before 1995, 26 (28%) between 1996 and 2000 and 56 (61%) between 2001 and 2005. Sixty patients (65%) were male and median age was 49 years ( range 21–68). Thirty-nine patients (42%) were older than 50 and 8 older than 60 years. Forty-four (48%) received myeloablative conditioning and 48 (52%) a RIC regimen. Myeloablative conditioning was based on cyclophosphamide plus thiotepa ( 42% of the patients) or busulfan (37%) or total body irradiation at the dose of 10–12 Gy (21%). RIC transplants consisted of a combination of fludarabine and 2 Gy TBI (44%) or cyclophosphamide (4%) or busulphan (4%) or an association of thiotepa and cyclophospamide (48%). GVHD prophylaxis included cyclosporin-A and short-course methotrexate, with the association of ATG in 11 patients. Stem cells came from matched sibling donors for 70 patients (76%), missmatched sibling donors for 10 patients (11%) and from matched unrelated donors for the remaining 12 patients (13%). Forty-nine patients (53%) received BM cells and the other 53 cases (47%) PBSC. Seventy-eight out 92 (85%) achieved full engrafment. One-year TRM was 35%. Causes of TRM were as following: GVHD (33% of the patients), infections (36%), bleeding (12%), veno-occlusive disease (3%), thrombotic thrombocytopenic purpura (6%). We observed a trend of higher TRM rate in patients transplanted before 2000 in comparison with those transplanted later (48% vs 33%). However, other potential risk factors for TRM, such as patient age > 50 years, conventional conditioning and unrelated or mismatched donors did not significantly increase TRM rate. There are 43 patients (47%) alive 12 to 156 months after transplantation ( median, 35 months).
We conclude that, albeit TRM rate has been lowered in transplants performed in the last 5 years, it still involves one-third of the patients and remains a matter of concern. The ongoing analysis will focus on the impact of the clinical and biological factors at transplant on the outcome of the patient population.
Alemtuzumab (CAMPATH®, MABCAMPATH®) Has Superior Progression Free Survival (PFS) vs Chlorambucil as Front-Line Therapy for Patients with Progressive B-Cell Chronic Lymphocytic Leukemia (BCLL).
Authors: Hillmen Peter , Skotnicki Aleksander , Robak Tadeusz , Jaksic Branimir , Sirard Cynthia , Mayer Jiri 
Published: October 2019

CAM307 is a phase III, open-label, multinational, randomized controlled trial comparing alemtuzumab (CAM) with chlorambucil (CHLO) for previously untreated BCLL requiring therapy. Eligible patients with Rai Stages I–IV were randomized 1:1 to either CAM 30 mg IV tiw for up to 12 weeks or CHLO 40 mg/m2 po q 28 days up to 12 cycles. CAM patients received prophylactic trimethoprim/sulfamethoxazole DS and famciclovir treatment during therapy and until CD4+ counts were ≥200 cells/μL. The primary endpoint was PFS; secondary endpoints were response rate, overall survival, and safety. A total of 297 patients were enrolled (CAM n=149 and CHLO n=148); median age: 60 years; performance status 0–1: 96%; maximum lymph node size ≥5 cm: 22%; and Rai Stage I–II: 63%, Rai Stage III–IV: 33%. Diagnosis, Rai Stage, response and disease progression were confirmed by an independent response review panel (IRRP). CAM has a significantly prolonged PFS compared to CHLO (p=0.0001; see KM survival curve).PFS in CAM vs CHLO patients with adverse cytogenetic findings of del 17p (n=21) was 10.7 mo vs 2.2 mo and for trisomy 12 (n=39) was 18.3 mo vs 12.9 mo. Results were similar for patients with del 11q (n=54, 8.5 mo vs 8.6 mo). Common (≥15%) CAM reported adverse events (AEs) (n=147), likely infusion-related, included pyrexia (70%), chills (53%), nausea (18%), hypotension (16%) and urticaria (16%). Common AEs (≥15%) in the CHLO arm (n=147) were nausea (37%) and vomiting (18%). Frequency of asymptomatic CMV viremia on the CAM arm was 52%; CMV infection occurred in only 16%, none grade 4. CAM treatment was interrupted in 56% of CMV viremic patients, and resumed in 92% with ORR 92% (31% CR). Ganciclovir was administered to 41% of CAM patients with CMV viremia. Infections, including CMV, were reported in 76% of CAM and 50% of CHLO patients while on study. Relevant grade 3/4 treatment-emergent events included (CAM vs CHLO): lymphopenia (97% vs 3%), pyrexia (8% vs 0%), CMV events (8% vs 0%) and chills (3% vs 0%). Treatment emergent grade 3/4 thrombocytopenia (16% vs 13%) and anemia (14% vs 19%) were similar, and although grade 3/4 neutropenia was more common with CAM, (45% vs. 26%), AEs of CAM vs CHLO bacteremia/sepsis (3% vs 2%) and febrile neutropenia (5% vs 3%) were comparable. Serious AEs were reported for 44% of CAM (20% for IV Ganciclovir only in CMV viremic patients) and 20% of CHLO patients while on study treatment. CONCLUSIONS: CAM307 demonstrates that therapy-naïve BCLL patients treated with CAM have significantly longer PFS and higher ORR than those treated with CHLO, with manageable toxicities. Although CMV reactivation was reported in the CAM arm, prompt intervention maintained efficacy. The activity seen here supports ongoing investigations of CAM in first line combination therapy, high risk patients and consolidation.
Figure Figure
Allogeneic Stem Cell Transplantation (Allo-SCT) for Relapsed/Refractory T Cell Lymphomas in Adults: A Survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).
Authors: Le Gouill Steven , Milpied Jean-noël , Vernant Jean-paul , Ifrah Norbert , Mechinaud Françoise , Gratecos Nicole , Chir Zina , Harousseau Jean-luc , Socié Gérard , Haioun Corinne , Blaise Didier , Michallet Mauricette 
Published: October 2019

Abstract
Background: Adult mature T-cell and NK-cell neoplasms include several lymphomas entities. Taken together, T- and NK- cell lymphomas represent 10–15 % of non-Hodgkin’s lymphoma in adults, presenting with aggressive behaviour and poor outcome (except for ALCL ALK positif lymphomas). Despite intensive chemotherapy including or not autologous stem cell transplantation upfront, a majority of patients experience relapse. Therefore, allo-SCT is an attractive second-line strategy. We retrospectively analyzed T-cell lymphomas patients (lymphoblastic lymphomas were systematically excluded) reported to the SFGM-TC registry and transplanted from an HLA identical sibling donor with or without myeloablative conditioning regimen.
Results: In the present intermediate report, we analysed 24 patients. Because of misdiagnosis, we excluded two cases. Among the 22 remaining patients, there were peripheral T-cell lymphoma NOS (PTCL) in 5 cases, angioimmunoblastic T-cell lymphoma (AITL) in 3 cases, anaplastic large cell lymphoma (ALCL) in 10 cases (ALK positif in 3 cases; negative in 2 cases and unknown in 5 cases; respectively), hepatosplenic g/d lymphoma (HSL) in 2 cases, T-cell granular lymphocytic leukemia (GLL) in 1 case and localized nasal NK/T cell lymphoma (NK/L) in one case. There were 15 males and 7 females. Median age was 38.5 years (15.5–54). All patients have been considered eligible for allo-SCT because of poor prognosis factors: HSL diagnosis in 2 cases, relapsed/refractory disease in 16 cases (including all ALCL cases) and/or failure to reach CR in 8 cases. Disease status at the time of transplantation was CR in 9 cases, PR in 7 cases and PD/refractory in 3 cases; respectively. All patients but 2 underwent myeloablative conditioning regimen prior to transplantation (TBI/EDX in 70%). The majority of patients (86%) received BMSC graft from related HLA-matched sibling donor. Median overall survival (OS) was 70 months for the all cohort. Median OS was not reached in the ALCL subgroup compared to 20 months for the non-ALCL subgroup. According to disease status, 7 out of 9 patients in CR at the time of transplantation are alive and in CR at the time of the analysis compared to 6 out of 13 in non-CR patients. Cause of death was AGVH in 2 cases, bacterial or fatal infections in 4 cases and relapse in 2 cases, respectively.
Conclusion: these preliminary results show that allo-SCT is a treatment of choice for refractory/relapsed T-cell lymphomas. Results are very encouraging in relapsed/refractory ALCL patients and highlight the role of graft versus T-cell lymphoma effect. Further analysis are required to identify prognosis factors and additional cases will be analyzed at the time of the meeting.
Superior Survival after Autologous vs. Allogeneic Hematopoietic Stem Cell Transplantation (HCT) for Diffuse Large B-Cell Lymphoma (DLBCL) Not Explained by Differences in Chemosensitivity.
Authors: Hayes-Lattin Brandon , Carreras Jeanette , Zhang Mei-Jie , van Besien Koen , Vose Julie M. , Lazarus Hillard M. , Rizzo J. Douglas , Hari Parameswaran 
Published: October 2019

Abstract
No randomized trials have compared autologous HCT (autoHCT) to allogeneic HCT (alloHCT) for DLBCL. We analyzed the outcomes of 916 patients (pts) (837 autoHCT and 79 alloHCT) ages 18–60yrs after a first autoHCT or HLA-identical sibling alloHCT for DLBCL between 1995 and 2003 reported to the CIBMTR. Pts receiving T-cell depleted allografts or reduced-intensity conditioning were excluded. There were significant baseline differences between the groups in disease stage, B symptoms, extranodal disease and marrow involvement. AlloHCT pts were significantly more likely to have >3 chemo regimens prior to HCT (53 vs 40%), and resistant induction failure or relapse (39 vs 16%). At 1yr, treatment-related mortality (TRM) was higher after alloHCT (41%, 95% CI, 30–52%) than after autoHCT (11%, 95% CI, 9–14%, p<0.001), but risks of relapse/progression were similar (30%, 95% CI, 21–41%) and (33%, 95% CI, 29–36%, p=0.69), respectively. Cumulative incidence of outcomes and univariate probabilities of progression free (PFS) and overall survival (OS) at 5 yrs are summarized in table 1. In multivariate analysis, allo and autoHCT had differential early and late effects on outcomes. In the first 12 mo after transplant, alloHCT was associated with higher TRM (RR 4.76, 95% CI, 3.14–7.22, p<0.001), treatment failure (RR 2.08, 95% CI, 1.56–2.77, p<0.001) and mortality (RR 2.78, 95% CI, 2.06–3.77, p<0.001) but similar risk of progression (RR 1.14, 95% CI, 0.75–1.74, p=0.54) compared to autoHCT. Among pts surviving 12 mo post-transplant, no significant difference was observed between autoHCT and alloHCT for TRM, progression, PFS, or OS. Covariates that increased the risks of TRM and OS were older age (51–60 years), KPS <90%, chemoresistance at transplant, and earlier transplant yr (before 2001 vs later). Older age and chemoresistance were also associated with progression and lower PFS. There were no significant interactions between graft type and other prognostic variables; in particular, relative risk of outcomes with allo vs autoHCT were similar for patients with chemosensitive and chemoresistant disease. In summary, myeloablative alloHCT increased risks of early TRM and mortaliy without an effect on progression (compared to autoHCT). Transplant type did not affect outcomes after 12 months post-transplant. AutoHCT was associated with superior survival (fig 1), and the difference was not explained by differences in chemosensitivity at the time of transplant.
AutoHCT AlloHCT Outcomes (95%CI) (95%CI) AGVHD @ day 100 N/A 42 (31–53) CGVHD @ 5yrs N/A 27 (18–38) TRM @ 5yrs 18 (15–20) 45 (34–57) Relapse/progression @ 5yrs 39 (36–43) 33 (23–44) PFS @ 5yrs 43 (40–46) 26 (18–37) OS @ 5yrs 49 (46–53) 27 (18–27) Figure 1 Figure 1.
Front-Line Autologous Stem Cell Transplantation (ASCT) in Primary Mediastinal Large B-Cell Lymphoma: The GEL-TAMO Experience.
Authors: Rodriguez Jose , Conde Eulogio , Gutierrez Antonio , Garcia-Ruiz Juan Carlos , Lahuerta Juan Jose , Varela Maria Rosario , Perez-Equiza Encarnacion , Marin Julian , Albo Carmen , Caballero Maria Dolores 
Published: October 2019

Abstract
From 1985 to 2006, 71 patients with primary mediastinal large B-cell lymphoma receiving induction doxorubicine-based chemotherapy followed by ASCT as front-line therapy were registered in the GEL-TAMO (Spanish Group for Lymphoma and Autologous Transplantation). Median age was 28 years, 56% of patients were female, 40% presented with an ECOG ≥ 2; B-symptoms at diagnosis were present in 25% of the patients. Most patients presented with high-risk clinical features: bulky tumours defined as ≥10 cms of diameter were observed in most patients (87%), high LDH in 72% and, as previously reported (Rodriguez et al, Ann Oncol, 1994), β2m was elevated only in 7% of the cases. Forty-seven percent of patients presented 2–3 risk factors of the a-IPI. At transplant, thirty-five patients (49%) in first complete remission (CR), 23 (33%) in partial response and 13 patients (18%) failing the first induction therapy were transplanted, respectively. Conditioning regimens were BEAM or BEAC in 90% of the patients. 39 patients received Radiotherapy: 19 prior and 20 after the transplant. Most patients (91%) received peripheral stem cells. Only a patient failed to engraft after the transplant. After the transplant 73% of the patients achieved a CR and 17 patients were refractory. With a median follow-up from transplantation of 46,5 months the OS, PFS and DFS are 68%, 59% and 81% respectively. Progression of the disease was the main cause of death (78%). A patient died of a second neoplasia and 3 patients died of sepsis. There were no deaths related to transplant toxicity. By multivariate survival analysis both status of the disease at transplant (CR vs PR vs failure) and the Tumor score (Rodriguez et al, Ann Oncol,1992 ) were the only independent variables associated with the OS and PFS, respectively. In conclusion our experience, with a prolonged follow-up, shows that patients with primary mediastinal large B-cell lymphoma presenting at diagnosis with high-risk features have an encouraging survival and PFS with front-line ASCT. However, patients who received the transplant having failed the induction regimen have a very poor prognosis and should be tested with another innovative approach.
Deletion of the Short Arm of Chromosome 1 (del 1p) Is the Strongest Predictor of Poor Outcome in Myeloma Patients Undergoing an Autotransplant.
Authors: Ahmed Bilal , Saliba Rima M. , Ashraf Noman , Mendoza Floralyn , Hosing Chitra , Flosser Thuy , Weber Donna M. , Wang Michael , Couriel Daniel R. , Popat Uday , Kebriaei Partow , Alousi Amin M. , Champlin Richard E. , Giralt Sergio A. , Qazilbash Muzaffar H. 
Published: October 2019

Abstract
Background: Chromosomal abnormalities detected by conventional cytogenetic analysis are known to adversely impact the outcome in myeloma patients. Abnormalities of chromosome 1, 13, 14 and 17 are commonly described. Deletions of the short arm of chromosome 1 presumably result in a loss of tumor suppressor genes, including p73, a member of the p53 family. We report the outcome of 83 myeloma patients with clonal cytogenetic abnormalities who underwent high-dose therapy and single autologous stem cell transplantation at our institution.
Methods: We identified 83 patients (median age: 56 years) with clonal cytogenetic abnormalities detected at diagnosis by conventional chromosomal analysis. Patients underwent high-dose therapy and a single autologous transplant between April 2000 and May 2005. All 83 patients received high-dose melphalan, either alone (73) or as a combination of topotecan, melphalan and cyclophosphamide (TMC =10). Sixty-four patients were transplanted for the consolidation of first remission or for primary refractory disease, while 19 patients were transplanted for relapsed disease. The most common chromosomal abnormalities observed were hyperdiploidy (21%), del 1p (19%), 14q32 abnormalities (14%) and del 13q (10%).
Results: Median follow up among surviving patients was 25.5 months. Median interval from diagnosis to autotransplant was 7.7 months (range 2.5–52). Median progression-free survival (PFS) for the entire group was 19 months and the median overall survival (OS) was 52 months. On univariate analysis, both PFS and OS were significantly shorter in patients with del 1p (p= 0.001 and <0.0001, respectively), and those transplanted with relapsed disease (p= 0.03 and 0.04). Median PFS and OS for patient with del 1p were 12 and 22 months (vs. 26 moths and not reached for others), respectively. Thirty-two patients whose cytogenetic abnormalities resolved prior to autotransplant had a trend towards longer OS than the patients with persistent abnormalities (p = 0.08). Age, disease stage, β2m, serum albumin level, serum creatinine, and isolated abnormalities of chromosome 13q, 17 and 14 q32 did not emerge as significant predictors of outcome in this set of patients.
Conclusion: Del 1p is associated with a significantly shorter remission and survival in patients undergoing high-dose therapy and a single autologous transplant. Patients with this abnormality are candidates for novel therapeutic approaches including newer antimyeloma drugs and nonablative allogeneic transplantation.
CD3/CD19 Depleted Grafts for Haploidentical Stem Cell Transplantation in Children: Results of a Pilot Study.
Authors: Lang Peter J. , Mueller Ingo , Greill Johann , Bader Peter , Schumm Michael , Pfeiffer Matthias , Feuchtinger Tobias , Handgretinger Rupert 
Published: October 2019

Abstract
Profound depletion of T and B cells is a fundamental prerequisite for haploidentical transplantation. We present our preliminary results with a direct depletion procedure using antiCD3/antiCD19 coated magnetic microbeads and the CliniMACS™ device. Only patients with high risk malignancies (n=25, most of them had active disease or relapsed after previous trp.) or with nonmalignant diseases and high risk of graft failure (n=2) were included. The diagnoses were: AML/MDS/CML (n=13), ALL(n=6), relapsed Neuroblastoma/Ewing-/Rhabdomyosarcoma (n=6), SAA, PNH (n=2); Remission status: NR=8, 2nd transplantation=10, CR/CP1=3, CR2–4=6.
The patients received either TBI or Bu based standard conditioning regimens (n=9) or a toxicity reduced protocol (Flud, TT, Mel, OKT3, MMF, n=18). The grafts comprised a median number of 16x106/kg (7–41) stem cells as well as high amounts of NK-cells (137x106 (9–550)) and monocytes/granulocytes (6x108 (0.6–13)) with 49x103/kg (7–200) residual CD3+ cells and <0.01% CD20+ cells. Primary engraftment occurred in 89% of patients (after reconditioning and second stem cell donation:100%). Median time to reach >500 neutrophiles/μl and independence from platelet substitution was 10 and 9 days respectively. Recovery of CD3+ cells was favorable (d90: 320/-l, d180: 600/μl). Acute GvHD grade 0–1 occurred in 74%, 26% had GvHD grade II. Limited chronic GvHD occurred in 4 patients. No transplant related mortality (TRM) and, in particular, no lethal infections were observed. 13/27 patients (49%) were alive with a median follow up of 0.8 years (3 months – 2.1 years). Single cause of death was relapse. Disease status was predictive: 8/9 patients with leukemias and active disease relapsed, whereas only 2/10 patients in CR relapsed. 2/6 patients with solid tumors are alive.
Recovery of platelets was faster in patients with CD3/CD19 depleted grafts than in a historical control group of patients (n=53) transplanted with haploidentical positive CD34+ selected standard grafts (23 vs. 9 days, p<0.01). No lethal viral infections occurred in the study group due to the fast T cell recovery, whereas in patients with positive selected grafts a cumulative incidence of 18% was observed. The toxicity-reduced conditioning regimen helped to avoid any other TRM, despite intensive pretreatment (including previous transplantation) of the patients.
Conclusions: our preliminary results indicate that CD3/CD19 selected grafts can improve immunoreconstitution and TRM. Engraftment rates similar to that of patients with myeloablative standard conditioning regimens and positive selected stem cells could be achieved, although most patients of the study group received an intensity reduced regimen. However, the outcome was poor in patients with active disease. Thus, further options have to be investigated to increase the potential antileukemic activity of donor derived effector cells.
Favorable Outcome of Patients with Relapsed Hodgkin Lymphoma (HL) after Nonmyeloablative Hematopoietic Cell Transplantation (NM-HCT) Using Related Haploidentical Donors.
Authors: O’Donnell Paul , Luznik Leo , Symons Heather , Jones Richard , Gooley Ted , Harrington Elizabeth , Warnock Sandra , Sandmaier Brenda , Storb Rainer , Fuchs Ephraim 
Published: October 2019

Abstract
NM-HCT from related donors who share at least one HLA haplotype with the recipient is a treatment option for patients with hematologic malignancies who do not have suitable HLA-matched related or unrelated donors. We have shown that addition of cyclophosphamide pre-transplant (29 mg/kg) and post-transplant (50 mg/kg on day+3 or days+3 and +4) to a standard nonmyeloablative conditioning regimen of fludarabine and TBI combined with tacrolimus and MMF prophylaxis of GvHD is an effective means of achieving complete engraftment of donor T-cells and granulocytes with low non-relapse mortality and an incidence and severity of acute and chronic GvHD which does not differ from studies of NM-HCT using HLA-matched donors. In a study of 89 patients (FHCRC,N=30; JH,N=59) with advanced myeloid and lymphoid malignancies, patients with relapsed HL had significantly better survival than patients with other diagnoses. Fifteen patients with HL were studied (median follow-up of 17 mo). Patients were heavily pre-treated with a median number of prior cytotoxic therapy regimens of 5 (range: 3–10); 14 patients had failed prior autologous HCT with a median time of 18 mo from auto-HCT to NM-HCT. Donors for 9 patients were HLA-mismatched at ≥4/10 loci. All evaluable patients were complete donor CD3 and CD33 chimeras by day +28 (one patient died on day +28 and was not evaluable). Clinically significant acute GvHD occurred in 9/14 (64%) patients and Grades III/IV GvHD in 3/14 (21%) patients. Extensive chronic GvHD occurred in 5/14 (36%) patients. Two patients (13%) died of non-relapse causes at days +236 and +633 secondary to chronic GvHD. Median failure-free survival (FFS) was 21 mo compared to 6 mo for patients with other lymphoid malignancies (N=23) or myeloid malignancies [(N=51), see Figure]. The hazard of mortality was less among patients with HL compared to those with other lymphoid malignancies [hazard ratio (HR)=0.36 (p=0.05)] yet patients with myeloid malignancies had a similar hazard of mortality compared to those with lymphoid malignancies other than HL [HR=0.88 (p=0.66)]. Difference in FFS between HL and other lymphoid malignancies was not statistically significant [HR=0.54 (p=0.16)], nor was the difference between myeloid and other lymphoid malignancies [HR=1.26 (p=0.44)]. More patients will need to be studied to better demonstrate a graft-versus-lymphoma effect of haploidentical transplantation in relapsed HL. NM-HCT from haploidentical donors may be a good option for such patients who have a limited window of opportunity to proceed to transplant if responsive to salvage chemotherapy.
Figure Figure Figure Figure