bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced-Intensity Conditioning Followed by Allogeneic Stem Cell Transplantation (allo-SCT) Is an Effective Salvage Treatment for Peripheral T-Cell Non-Hodgkin’s Lymphoma (PTCL).
Authors: Corradini Paolo , Dodero Anna , Bregni Marco , Zallio Francesco , Farina Lucia , Rambaldi Alessandro , Patriarca Francesca , Olivieri Attilio , Bonifazi Francesca , Gianni Alessandro Massimo , Tarella Corrado 
Published: April 2020

Abstract
Patients with relapsed PTCL have a poor prognosis. We had previously shown the existence of a graft-versus-lymphoma effect against PTCL (J Clin Oncol, 2004). In the present report, we extended our previous observations to 26 patients (pts) receving allo-SCT. All patients received several courses of debulkying chemotherapy (usually 3 DHAP and/or high-dose chemotherapy) followed by the same RIC regimen containing thiotepa (10 mg/kg), fludarabine (60 mg/ms) and cyclophosphamide (60 mg/kg). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. Patients’ median age was 45 years (range, 15–64). Histologic PTCL subtypes included: PTCL not otherwise specified (n=12), ALCL (n=7), angioimmunoblastic (n=3), others subtypes (n=4). Twenty-two pts (84%) received transplant from HLA-identical sibling, 3 from haploidentical sibling and one from unrelated donor. The median time from diagnosis to transplantation was 17 months. Thirteen patients (50%) had failed a previous auto and the majority received at least 2 lines of chemotherapy before allo-SCT. Seven (27%) and 13 pts (50%) were in CR and PR at the time of allo-SCT, respectively. At median follow-up of 27 months (range, 8–73), 17 (65%) were alive (n=14 in CR) and 9 died (n=6 disease, n=3 toxicity). The estimated 3-year TRM was 13%. The estimated 5 year OS and PFS projections were 61% (95% CI, 41–81%) and 51% (95% CI, 30–72%), respectively. Relapses occurred in the first 6 months after allo-SCT and we did not observe differences in PFS between specified and unspecified variants. De-novo acute GVHD (II/IV) and chronic GVHD incidence were 28% and 24%, respectively. Eight patients received DLI, 6 for relapse, 1 pre-emptive, 1 for infection: 3 responded (n=1 CR, n=2 PR). Following DLIs, 4 patients developed GVHD with associated a clinical response. In conclusion, our data indicate: 1) long-term disease control was achieved in patients with an aggressive subtype of NHL; 2) although optimal therapeutic strategies for relapsed PTCL are yet to be defined, further prospective evaluation of allo-SCT is required.
Reduced-Intensity Conditioning (RIC) Followed by Allogeneic Stem Cell Transplantation (SCT) for Relapsed Lymphomas: Impact of Pre-Transplantation Factors on Long-Term Outcome.
Authors: Corradini Paolo , Dodero Anna , Bregni Marco , Ciceri Fabio , Olivieri Attilio , Farina Lucia , Valagussa Pinuccia , Scime’ Rosanna , Locasciulli Anna , Patriarca Francesca , Gianni Alessandro Massimo , Tarella Corrado 
Published: April 2020

Abstract
Allogeneic stem cell transplantation (SCT) represents a potentially curative treatment for recurrent lymphoid malignancies. In fact, potential advantages include the use of a tumor free graft and immune-mediated graft-versus-lymphoma effect. Here, we analyzed the impact of pre-transplantation factors on outcome in 141 lymphoma patients (pts) receiving RIC and allogeneic SCT from HLA-identical sibling donors. Histologic types included in the study were: low-grade non-Hodgkin lymphoma (LG-NHL; n=58), high-grade NHL (HG-NHL, n=55), Hodgkin disease (HD; n= 28). Median age was 50 years (range: 20–69). The three groups (HD vs LG-NHL vs HG-NHL) had similar characteristics in terms of: chemosensitive disease (57% vs 69% vs 67%, p=ns) and complete remission (CR) at transplant (18% vs 27% vs 34%, p=ns). Pts with HD had received more lines of chemotherapy (&gt;2 vs ≤2) as compared to LG-NHL and HG-NHL (82% vs 52% vs 42%). Furthermore, the proportion of pts receving previous autologous SCT was significantly higher in HD and HG-NHL versus LG-NHL (75% vs 54% vs 27%). In addition, patients with HG-NHL and HD underwent frequently allo-SCT less than 2 years after diagnosis as compared to LG-NHL (58% vs 39% vs 24%). All patients received debulkying chemotherapy followed by the same RIC containing thiotepa (10 mg/kg), fludarabine (60 mg/ms) and cyclophosphamide (60 mg/kg). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. At a median follow-up of 30 months (8–70), the overall survival (OS) and progression-free survival (PFS) were 65% (95%CI, 56–74%) and 57% (95%CI, 47%–67%), respectively. Univariate analysis showed that age (&lt; or &gt; 55 years), donor sex, interval between diagnosis and SCT, number of previous treatments did not influence outcome whereas diagnosis of HD was associated with a significant inferior PFS and OS. Chemosensitive disease (CR+PR) influenced PFS in HG-NHL (p&lt;0.0003) and HD (p&lt;0.0036) but not in LG-NHL (p=0.69). Complete remission at transplant was associated to a significant better PFS in HD (p&lt;0.01) but not in HG-NHL (p= 0.14) and LG-NHL (p=0.7). Previous autologous SCT was associated to inferior PFS (64% vs 50%, p&lt;0.04) but did not affected OS and TRM. By multivariate analysis, diagnosis of HD and refractory disease were associated to an inferior PFS (p&lt;0.0001, p&lt;0.001) whereas diagnosis of HD and no-CR at transplant remained of prognostic value on OS (p&lt;0.006 and p&lt;0.007). We conclude: 1) age and previous treatments, including autologous SCT, are no longer limitations for allogeneic SCT; 2) debulking therapy before RIC allogeneic SCT is required for HD and HG-NHL; 3) new strategies for an early indentification of chemorefractory pts are necessary.
Allogeneic Stem Cell Transplantation (allo-SCT) from a HLA Identical Sibling for CR1 AML Patients Aged above 55 Years Old after a Reduced Intensity Conditioning: A Survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).
Authors: Blaise Didier , Chir Zina , Attal Michel , Bourhis Jean-Henri , Sotto Jean-Jacques , Boiron Jean-Michel , Milpied Noel , Cahn Jean-Yves , Rio Bernard , Lioure Bruno , Guilhot Francois , Berthou C. , Buzyn Agnes , Michallet Mauricette 
Published: April 2020

Abstract
Background: AML incidence increases with age. Allogeneic stem cell transplantation (Allo-SCT) offers the best leukemic control but is associated with high non-relapse mortality (NRM). Recent advances using non-myeloablative strategies have established the feasibility of allo-SCT in elderly patients. However in the context of AML, an important reduction of the intensity of the preparative regimen may be also associated with a loss of leukemic control, offsetting the impact of toxicity reduction in elderly.
Methods: We retrospectively analyzed AML patients in first complete remission (CR1) reported to the SFGM-TC, aged above 55 and transplanted from a HLA identical sibling donor prior to 01/01/05.
Results: 62 patients prepared with a non-myeloablative conditioning (NMAC) (fludarabine (75mg/m2) + TBI (2Gy)) (N=14) or a reduced intensity conditioning (RIC) (busulfan (4 to 8 mg/m2) + fludarabine (150 to 180 mg/m2) + thymoglobulin (2.5 to 12.5 mg/m2)) (N=48). GVHD prophylaxis used CSA+MMF for NMAC, CSA +/− MMF for RIC. With few exceptions, all patients in a given centre were treated identically. Major characteristics were: age 58 (55–67), M/F= 27/35. Time between diagnosis and allo-SCT: 171 days (101–467). BMT/PBSCT: 7/55. Pts have been considered for allo-SCT because of poor prognosis factors: no favorable cytogenetics (100%), secondary AML (15%), 2 chemotherapy course to achieve CR1 (24%) or M0, M6 or M7 FAB (20%). All pts engrafted. Acute GVHD occurred in 16 pts (grade 1: 6; grade 2: 6; grade 3–4: 4) and chronic GVHD in 18 pts (limited: 8; extensive: 10) with no difference in the 2 groups. The cumulative incidences of grade 2–4 aGVHD and cGVHD were 16% (95%CI: 7–25) and 29% (95%CI: 18–40) respectively. 15 pts relapsed and 8 died from NRM. Relapse and NRM cumulative incidences were 24% (95%CI: 13–35) and 13% (95%CI: 5–21) respectively. 49 pts were evaluable for cGVHD: of the 18 expressing cGVHD none have relapsed as compared to 12 of the 31 who did not present cGVHD (39%, 95%CI: 22–56) (p=.007). The 2 year KM survival and DFS probabilities are 63% (47–76) and 56% (42–69). In a landmark analysis investigating patients alive on day 100, 2 year DFS are 94% and 38% respectively with or without cGVHD (p=0.001) and 2 year KM OS are respectively 94% and 45% (p=0.01).
Conclusions: We conclude that such a strategy in elderly can afford a high relapse control with low NRM conducting to high survival probability at 2 years. Results are achieved through the allogeneic effect as expressed by cGVHD inviting to a careful immunomodulation in the early post transplant period to further improve results.
Arkansas Autotransplant (AT) Experience with &gt; 2500 Myeloma (MM) Patients: Follow-Up Extending to &gt;15 Years.
Authors: van Rhee Frits , Tricot Guido , Anaissie Elias , Reiner Maureen , Zangari Maurizio , Burns Michael , Epstein Joshua , Shaughnessy John , Rasmussen Erik , Crowley John 
Published: April 2020

Abstract
Background: AT’s have become the standard of care for MM. Long-term follow-up studies from large centers are critical to understand who benefits most and who should be considered for alternative treatment approaches.
Patients and Methods: 2,605 MM patients receiving at least one AT at the University of Arkansas were considered for this study. Kaplan-Meier analysis was used to estimate median event-free (EFS) and overall survival (OS). Cox regression was used to evaluate independent prognostic factors of EFS and OS from AT.
Results: Of the 2,605 patients, 891 were enrolled into front line Total Therapy (TT) protocols TT1/2/3 (TT); 1,012 were treated on protocols for previously treated patients (non-TT); and 702 were treated off protocol due to significant co-morbidities or patient/MD preference (non-P). Median EFS and OS for all patients are 29 mo and 51 mo; 10-yr EFS and OS are 18% and 23%; 12% survived &gt;15yr. Features independently predicting superior survival included TT (HR 0.51, p&lt;.001), absence of cytogenetic abnormalities (no CA) (HR 0.47, p&lt;.001), timely application of 2nd transplant (&lt; 6 months of 1st transplant) (HR 0.71, p&lt;.001) as well as B2M &lt; 3mg/L, CRP &lt; 6mg/dL, albumin &gt;=3g/dL, platelet count &gt;=100.000/microL (all p&lt;.001) and age &lt;65yr (p=.008). The figure depicts survival (landmarked at 6 months after 1st transplant) according to the number of favorable features present of the 5 strongest predictors (TT, 2 transplants within 6 months, no CA, low B2M, low CRP).
Conclusion: This large single institution experience demonstrates that &gt; 10yr survival can be accomplished in over one-half of the patients presenting without CA (14%), with low levels of B2M and CRP and receiving TT and timely 2nd autotransplant. The worst constellation affected 5% of all patients presenting with at most 1 good-risk feature whose 5-yr survival was only 8%. Collectively, these data should serve as a standard for MM investigators and patients alike, against which long-term outcome of newer treatments should be measured.
Figure Figure
The Time Required To Achieve Complete Remission (CR) during Intensive Therapy on Total Therapy 2 Does Not Influence Event Free Survival (EFS), While Improvement in Quality of Response with Ongoing Treatment Clearly Does.
Authors: Tricot Guido , Reiner Maureen , Zangari Maurizio , van Rhee Frits , Anaissie Elias , Milner Teresa , Barlogie Bart 
Published: April 2020

Abstract
In acute leukemia and intermediate/high grade lymphoma it is important to achieve a CR as early as possible. The aim of the study was to evaluate if the same is true in myeloma treated with intensive therapy including tandem transplants (Tx-1; Tx-2). A total of 668 patients were enrolled on our Total Therapy 2 protocol, which randomized patients upfront to intensive therapy with or without thalidomide. The protocol consisted of 4 induction cycles followed by tandem transplants, 1 year of consolidation chemotherapy and maintenance therapy with dexamethasone pulsing every 3 months for 1 year and interferon-α, if tolerated. This study is limited to the 570 patients who received at least one transplant. CR was defined as absence of serum and urine M-protein with negative immunofixation electrophoresis and &lt; 5% bone marrow plasma cells. EFS analyses were performed using Kaplan-Meier plots and log rank statistics to compare different groups. A 1 year landmark after Tx-1 was employed to compensate for guaranteed time of CR patients. Prior to Tx-1 89 patients (16%) were in CR, 111 in near CR (nCR), 110 in partial remission (PR) and 260 in &lt; PR. After Tx-1, 170 (30%) achieved CR, 159 nCR, 116 PR and 125 &lt; PR. The ultimate best response was CR in 319 patients (56%), nCR in 134, PR in 68 and &lt; PR in 49. EFS of patients ultimately achieving CR was similar for those who were either in CR, nCR, PR or &lt; PR prior to Tx-1 (p=0.47; Fig 1a). Patients in PR prior to Tx-1, but ultimately achieving CR or nCR faired considerably better than those who remained in PR (p=0.003 Fig 1b). Similarly, EFS of patients ultimately achieving CR was comparable for those who were either in CR, nCR, PR or &lt; PR prior to Tx-2 (p=0.53). The same observations were made for both patients randomized to thalidomide or no thalidomide, or with and without baseline metaphase cytogenetics. With a median follow-up of 3 year after Tx-1 no difference in EFS was seen relative to the timing of achievement of CR. However, improvement of quality of response with further therapy resulted in a significant increase in EFS, strongly suggesting additional benefit from the second transplant and consolidation chemotherapy.
1a Event-Free Survival Comparing best Response Before TX1 To Best Response Overall (Landmark 12 months posts TX1) 1a. Event-Free Survival Comparing best Response Before TX1 To Best Response Overall (Landmark 12 months posts TX1) 1b Event-Free Survival Comparing best Response Before TX1 To Best Overall Landmark 12 months posts TX1 1b. Event-Free Survival Comparing best Response Before TX1 To Best Overall Landmark 12 months posts TX1
Flow Cytometric Detection of Circulating Myeloma Cells Pretransplant in Patients with Multiple Myeloma: A Simple Risk Stratification System.
Authors: Dingli David , Nowakowski Grzegorz S. , Dispenzieri Angela , Lacy Martha Q. , Hayman Suzanne R. , Rajkumar Vincent S. , Greipp Philip R. , Litzow Mark R. , Gastineau Dennis A. , Witzig Thomas E. , Gertz Morie A. 
Published: April 2020

Abstract
Background: The presence of circulating myeloma cells (CMC) detected by flow cytometry at the time of diagnosis of multiple myeloma is associated with a shortened response to therapy and reduced overall survival (OS). We hypothesized that the presence of CMC at the time of stem cell collection prior to high dose therapy (HDT) and autologous stem cell transplantation (ASCT) would identifies a cohort of patients with a high risk of rapid progression.
Methods: The Mayo Clinic myeloma transplant database was queried for patients who were mobilized using cyclophosphamide and hematopoietic growth factors. CMC was determined using flow cytometry by gating on a population of CD38 bright and CD45 negative cells. The impact of CMC on OS and time to progression (TTP) and its role in the context of established prognostic parameters was evaluated.
Results: Of 246 patients with MM undergoing ASCT, 95 had CMC. Patients with CMC had significantly higher plasma cell labeling index, adverse cytogenetics, B2-M and resistant disease. Complete response (CR) rates post transplant were 32% and 36% for patients with and without CMC (p=0.5034). OS was 33.2 and 58.6 months (p=0.0052) while TTP was 14.1 and 22 months respectively (p=0.0005).
Figure Figure
On multivariate analysis, CMC remained an independent prognostic factor in a model that included cytogenetics and disease status at time of transplant (p=0.0314). A prognostic system based on the presence or absence of CMC and karyotype abnormalities was developed. Patients with neither, one or both parameters had a median, OS of 55, 48 and 21.5 months respectively (p&lt;0.0001) while TTP was 22, 15.4 and 6.5 months for the same groups (p&lt;0.0001).
Conclusion: The presence of CMC at the time of HDT and ASCT is an independent prognostic factor. The combination of CMC and cytogenetics provides a simple yet powerful scoring system that stratifies patients and guides their management.
The Role of Stem Cell Mobilization Regimen on Lymphocyte Collection Yield and Survival after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.
Authors: Porrata Luis F. , Hayman Suzanne R. , Gertz Morie A. , Lacy Martha Q. , Dispenzieri Angela , Kumar Shaji K. , Litzow Mark R. , Inwards David J. , Ansell Stephen M. , Micallef Ivnna N. , Johnston Patrick B. , Gastineau Dennis A. , Tefferi Ayalew , Elliot Michelle , Hogan William J. , Markovic Svetomir N. 
Published: April 2020

Abstract
We previously have reported that autograft absolute lymphocyte count (A-ALC) is a possible prognostic factor for survival after autologous peripheral blood stem cell transplant (ASCT) for myeloma (MM). Factors affecting A-ALC in MM are unknown. We hypothesize that method of stem cell mobilization, hematopoietic growth factor (HGF) vs. HGF+Cytoxan chemotherapy (C+HGF), directly affects A-ALC collection. 191 consecutive MM patients between 1994 and 2004 were analyzed retrospectively. Patients generally were mobilized with C+HGF prior to 2003. Thereafter, C+HGF was reserved largely for those with ≥4% circulating peripheral blood plasma cells (PC), a negative prognostic indicator. No patients were transplanted in disease relapse or refractory disease. Patients also were matched for age, sex, β2-microglobulin, conventional cytogenetics, LDH, c-reactive protein, number of prior therapies, plasma cell labeling index (PCLI), pre-mobilization ALC, and % bone marrow (BM) PC. The groups HGF (n=80) and C+HGF (n=111) differed with respect to the conditioning regimen (p &lt; 0.0001), and presence of (≥4%) circulating peripheral blood PC (p&lt;0.005). The primary end-point of the study was to assess the correlation between HGF vs C+HGF, and A-ALC. The secondary endpoint was to determine if HGF vs C+HGF affected survival post-ASCT. Patients mobilized with HGF had a higher A-ALC compared to those mobilized with C+HGF [0.764 x 109 lymphocytes/kg (range: 0.146–1.803) vs. 0.212 (range: 0.016–1.26), p&lt;0.0001]. No association was identified between A-ALC and conditioning regimens (p = 0.19) and PC (p = 0.31). Median overall survival (OS) and progression-free survival (PFS) were longer in those mobilized with HGF vs. C+HGF (not reached vs. 48 months, p&lt;0.0150; not reached vs. 21 months, p&lt;0.007, respectively). Multivariate analysis demonstrated that age ≥50 vs age ≤50 (p&lt;0.05) and A-ALC ≥0.5 vs &lt;0.5x109 lymphocytes/kg (p&lt;0.0397) were independent predictors of OS. Factors influencing PFS in the multivariate analysis included circulating PC ≥4% vs &lt;4% (p&lt;0.0157), PCLI ≥ 1% vs PCLI ≤ 1% (p&lt;0.0107), and A-ALC ≥0.5 vs &lt;0.5x109 lymphocytes/kg (p&lt;0.0042). On multivariate analysis, the method of stem cell mobilization and the conditioning regimen did not have a statistically significant effect on either OS or PFS. We hypothesize that the differences in PFS and OS seen between the HGF vs C+HGF mobilization groups are mediated through the A-ALC. These data suggest that mobilization regimens should not only collect CD34+ stem cells, but also be optimized to collect an A-ALC target which may impact on PFS and OS post-ASCT.
Transplant Outcomes after Topotecan-Melphalan-Cyclophosphamide (TMC) Conditioning for Autologous Stem Cell Transplantation for Multiple Myeloma. Comparison to Melphalan 200 mg/M2 (MEL200).
Authors: Donato Michele , Aleman Ana , Weber Donna , Wang Michael , Qazilbasch Muzaffer , Davis Marilyn , Roden Linda , Mendoza Floralyn , Champlin Richard , Giralt Sergio 
Published: April 2020

Abstract
Background: Topotecan at modest doses has activity in multiple myeloma (MM). The combination of high-dose topotecan, melphalan, and cyclophosphamide (TMC) has been used as a conditioning regimen for autologous SCT in patients with MM. We report the results of a phase II trial with this combination and perform a retrospective analysis comparing TMC to a standard preparative regimen of melphalan 200 mg/m2 (MEL200).
Patients and Methods: Between 10/99 and 3/04, 55 patients with newly diagnosed MM were treated on a Phase II trial of topotecan 3.5 mg/m2 daily for 5 days in combination with cyclophoshamide 1 gm/m2 daily for 3 days, and melphalan 70 mg/m2 daily for 2 days followed by autologous SCT. Patient characteristics are summarized in table 1. In brief, median age was 55 (range, 37–67), median time to transplant was 6 months (range, 2-59); median B2M @diagnosis 3.3 (range, 1.4–17.2); 76% of patients had chemosensitive disease prior to transplant.
Results: No treatment related deaths were observed, the regimen was well tolerated with grade 2 Bearman mucositis and diarrhea the most common toxicities, and no grade 3 or 4 toxicities observed. When compared to a group of patients who received MEL 200 the overall response rate was lower 75% vs 82% and a lower CR rate 11% vs 36%, but a similar median time to disease progression (14 m vs 13 m), with a trend towards a better 3 yr overall survival (87% vs 77%; p=.05) (Table 2 and Figure 1).
Conclusion: TMC is a well tolerated conditioning regimen for myeloma, our results suggests that although no more effective than MEL200 as a single preparative regimen for MM, it warrants exploring as part of a tandem transplant program.
Patient Characteristics TMC MEL200 N 55 157 Median Age (range) 55(37-67) 56(29-75) Median B2M @Dx 3.3 (1.4 - 17.2) 4 (0.5 - 49.8) % Abn Cytogenetics 15% 22% CR/PR @ SCT 4%/73% 10%/89% % 1ry Refractory 24% 27% Transplant Outcomes TMC MEL200 p ORR/CR conversion 75%/11% 82%/36% Non Relapse Mortality 0 2 Median OS NR 52 months .05
Figure Figure