bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alloreactive Alleles for the IL-10 -1064 Polymorphism in the Donor Associate with Chronic GVHD, in a Chimerism Mediated Fashion, after HLA Identical Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Manzano Cintia , Sanchez-Hernandez Noemi , Barroso Diana , Balsalobre Pascual , Gonzalez-Rivera Milagros , Serrano David , Carrion Rafael , Gomez-Pineda Alfonso , Diez-Martin Jose L. , Buño Ismael 
Published: October 2019

Abstract
Background: Polymorphisms in regulatory sequences of cytokine genes are known to influence their expression and, therefore, the intensity of the immune response. Some of such polymorphisms have been associated with the outcome of allogeneic stem cell transplantation (SCT).
Objective: To evaluate the association between donor (D) and recipient (R) genotype for the IL-10 gene -1082 SNP (single nucleotide polymorphism) and -1064 STR (short tandem repeat) polymorphism with the dynamics of chimerism and the development of complications after SCT.
Patients and methods: 24 HLA-matched conventional SCT. IL-10 genotypes were determined in an -1082 SNP allele-specific PCR (A vs G) including the -1064 STR in the product which is revealed by capillary electrophoresis. Results were analyzed using Fisher’s exact test due to the reduced sample size.
Results: The frequency of alloreactive genotypes (AA or A) for the SNP was 37,5% AA and 79,2% A in the D and 33,3 AA and 95,8% A in the R. No association was observed between the homozygous or heterozygous presence in the D or R of the alloreactive allele for the SNP genotype and the dynamics of chimerism or complications post-SCT. Alleles 4 to 10 for the STR genotype were found in contrast to previous reports (alleles 7–16). The frequency of alloreactive alleles (homozygous, +/+, or heterozygous, +), with greater number of dinucleotide repeats (alleles 8–10 in the present series) for the STR was 8,3% +/+ and 62,5% + in the D and 8,3% +/+ and 50% + in the R. The presence of alloreactive alleles (heterozygous) in the donor was significantly associated with the development of extense chronic GVHD (EcGVHD, Table 1). In patients transplanted from such donors, the incidence of mixed chimerism (MC) in peripheral blood during the first month post-SCT was lower although without statistical significance (Table 1). The higher alloreactivity of these donors favors the establishment of complete chimerism and therefore, increases the incidence of EcGVHD.
Conclusions: The present study shows an association between the presence in the donor of alloreactive alleles for the IL-10 -1064 STR polymorphism and the development of EcGVHD, in a chimerism mediated fashion, after HLA- identical SCT. The analysis of a larger number of patients as well as further cytokines will eventually allow to confirm these observations and to establish this type of studies as a means for an improved management of transplanted patients.
Table 1. Influence of alloreactive alleles (8–10) for the IL-10-1064 STR polymorphism on chimerism and complications post-STC.
Lactate Dehydrogenase (LDH) Level Predicts the Outcome of Patients with Acute Myelogenous Leukemia (AML) Following HLA-Matched Sibling Bone Marrow Transplant (BMT).
Authors: Kalaycio Matt , Rybicki Lisa , Pohlman Brad , Dean Robert , Sweetenham John William , Andresen Steven , Sobecks Ronald , Sekeres Mikkael A. , Advani Anjali , Davis Randall , Brown Stacey , Bolwell Brian 
Published: October 2019

Abstract
Active disease (ActDis), poor-risk cytogenetics, and older age have historically been considered the most important adverse risk factors for survival after BMT for AML. We performed a multivariable analysis of these and other potential risk factors for overall and progression-free survival. From August 1992 to July 2005, we treated 87 patients with AML, who also had informative cytogenetic studies, with high-dose busulfan-containing preparative regimens and an HLA-matched sibling BMT. The median age was 43 years (range 19 to 62). The median LDH level at the time of BMT was 204 U/L (range 93–1555 U/L; normal 100–220 U/L). Forty-one patients were in either first (n= 30) or second complete remission (n=11; CR). 46 patients with ActDis were treated. The 87 patients were then classified according to the SWOG/ECOG (Blood96:4075, 2000), MRC (Blood92:2322, 1998), and CALGB (Blood100:4325, 2002) cytogenetic classification systems. With a median follow-up of 56.0 months (range 4.5–107.8 months), the median relapse-free survival is 13.5 months for patients in CR1 and 4.1 months for patients in CR2. The relapse-free survival of patients with ActDis was 5.5 months. A Cox proportional hazards analysis that included gender, age, LDH, disease status, cytogenetic risk group, preparative regimen, source of stem cells, and CMV status was performed for overall and relapse-free survival. Significant risk factors for shorter survival in univariate analysis included male gender, LDH >330 U/L (but not LDH >220 U/L or per 100 U/L increase), and peripheral stem cells as a source of hematopoietic reconstitution (n = 7). Surprisingly, a male donor to a male recipient was also an adverse risk factor (p<0.001). However, in multivariable analysis, only LDH >330 U/L (p=0.002), source of stem cells (p=0.019), and male donor to male recipient (p<0.001) remained as significant adverse risk factors. In fact, patients with ActDis and an LDH ≤ 330 U/L had similar survival to patients treated in remission, while patients with ActDis and LDH > 330 U/L had significantly worse survival as shown below. We conclude that high LDH (>1.5X upper limit of normal) is a significant adverse risk factor for survival after BMT for AML and predicts outcome better than more traditional risk factors such as age, disease status, and cytogenetic risk profile.
Figure Figure
Polychemotherapy in Combination with Thalidomide Followed by Autologous or Allogeneic Transplantation for Rescue after Autograft or Induction Therapy Failure in Patients with Multiple Myeloma.
Authors: Hegenbart Ute , Schonland Stefan O. , Moehler Thomas , Benner Axel , Gerull Sabine , Goerner Martin , Schaefer Hans-Joerg , Egerer Gerlinde , Dreger Peter , Ho Anthony D. , Goldschmidt Hartmut 
Published: October 2019

Abstract
BACKGROUND: Most patients (pts) undergoing high-dose therapy and autologous transplant for multiple myeloma (MM) develop disease recurrence. The optimal salvage treatment for these patients is not well defined. Autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (SCT) have been used for salvage therapy.
METHODS: We performed a retrospective analysis of pts with MM (n=118) treated in our institution who had failed after 1st-line therapy or relapsed after auto-SCT. Re-induction was performed with TCED (thalidomide, cyclophosphamide, etoposide and dexamethasone, median number of cycles 3). Seventy-four pts (median age, 59 yrs) received auto-SCT as salvage therapy, whereas 44 pts (median age, 53 yrs, p=0.43) underwent a reduced-intensity allo-SCT (related in 23 pts), using conditioning with 2 Gy total body irradiation and fludarabine in 40 pts or melphalan 140 mg/m2 / fludarabine in 4 pts. The majority of the pts (37 / 44) received allo- SCT a median of 59 (range 33–186) days after auto-SCT. Twenty pts in the auto-group and 9 pts in the allo-group were primary progressive, respectively (p=0.42).
RESULTS: 89 pts (75%) responded to TCED chemotherapy (CR 4 pts, PR 65 pts, MR 22 pts, SD 13 pts). The number of pts progressing after TCED was equal in both groups (p=0.54). Remission status improved in 30 pts after auto-SCT (7 CR) and in 20 pts after allo-SCT (16 CR, p=0.001). After a median follow-up of 24 months for the auto-group and 21 months for the allo-group since the end of TCED therapy, the median event-free survival (EFS, figure 1) and overall survival (OS, figure 2) were 14 months in both groups (p=0.37) and 27 months versus 35 months (p=0.75), respectively. Incidence of chronic GvHD was 82% (62% extensive). TRM was 20% in the allo-group and differed significantly from the auto-group (1%, p=0.007). Three years after end of TCED 12/44 pts are alive (6 pts in CR) in the allo-group compared to 15/74 pts (1 pt in CR) in the auto-group. All but 1 pt with CR > 3 years after allo-SCT have extensive cGvHD.
CONCLUSIONS: Both auto- and allo-SCT are feasible as salvage therapy for MM. Disease recurrence or progression remains the major cause of treatment failure. More CRs and more long term survivors in CR have been observed after allo-SCT confirming the contribution of the GvM-effect. Further concepts are necessary to maintain CR, to prevent relapse or progression and to reduce TRM after allo-SCT.
Figure Figure Figure Figure
Fludarabine-Busulfan Conditioning and In Vivo T-Cell Depletion with Reduced Dose of ATG Followed by Allografting Induces Durable Responses in Patients with Advanced Multiple Myeloma with No Grade III-IV aGvHD.
Authors: Bahlis Nizar J. , Stewart Douglas A. , Savoie Mary Lynn , Brown Christopher , Daly Andrew , Chaudhry Ahsan , Storek Jan , Russell James A. 
Published: October 2019

Abstract
Background: We have investigated a conditioning regimen with Fludarabine and intravenous Busulfan with reduced ATG dose in patients with advanced and poor prognosis myeloma exploring the possibility that a low dose ATG may be sufficient enough to prevent severe GvHD without completely suppressing the graft vs myeloma effect.
Methods: 15 patients received a conditioning regimen consisting of fludarabine 50mg/m2 on days -6 to -2 and IV BU (Busulfex, ESP Pharma) at a “myeloablative” dose of 3.2 mg/kg daily days -5 to -2 inclusive. All pts received Thymoglobulin (Genzyme) 4.5 mg/kg in divided doses over 3 consecutive days pre-transplant finishing D0, cyclosporine A and methotrexate with folinic acid.
Results: The median age was 49 years (range 40–61). 14 (93.3%) patients had stage III (DS) disease with a median β2-microglobulin 3.12 mg/dl (1.82–5.75) and 7/11 (63.6%) in whom FISH studies were available had deletion 13, 5/15 (33.3%) patients had relapsed or progressed within 2 years of prior autologous stem cell transplant and 4 (26.6%) had progressed while on thalidomide /Dex salvage treatment. The disease status prior to allogeneic transplant was partial response (PR) in 6/15 (40%) and progressive disease (PD) in 9/15 (60%). 2/15 had plasma cell leukemia. The median number of bone marrow plasma cells prior to allo-transplant was 16% (range 3%-85%). Donors were matched siblings (MRD) for 13 (86.7%) and alternate donors in 2 (13.3%, unrelated with 2 C antigen mismatch). Cell source was blood in 14/15 (93.3%). Acute GVHD grade II-IV occurred in only 1 patient (6.6%) with no grade III-IV acute GVHD. Chronic GVHD occurred in 9/15 (60%). The TRM was 6.6%. Among 14/15 patients evaluable for response, the overall response rate (CR+PR) was 53.3% (2 CR, 6 PR, 1 MR and 5 PD); 37.5% (1CR, 2PR, 1MR and 4PD) for pts with PD at the time of the transplant and 71.4% (4PR, 1MR and 1PD) for pts with del13. After a median follow-up of 40.9 months (range 36–65.2), the estimated OS and PFS at 4 years for all patients is 38.9% (CI 95%: 13.1–64.7%) and 20.0% (CI 95%: 0–40.3%) respectively. For patients with del13 the estimated OS and PFS at 4 years is 38.1% (CI 95%: 0–77.9%) and 0% respectively.
Conclusion: In vivo T-cell depletion with ATG results in a low rate of severe aGvHD with low treatment-related mortality and a substantial number of long-term survivors among patients with advanced multiple myeloma. The detection of deletion 13 by FISH however remains a predictor of short progression free survival.
Figure Figure
Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients - A Single Center Study.
Authors: Stadler Michael , Hertenstein Bernd , Krauter Juergen , Buchholz Stefanie , Dammann Elke , Eder Matthias , Ganser Arnold 
Published: October 2019

Abstract
Allogeneic hematopoietic cell transplantation (alloHSCT) has curative potential in many hematologic malignancies; however, substantial treatment related toxicity has restricted its use to younger patients (mostly under 55 years of age). With the development of conditioning regimens of reduced intensity, alloHSCT is being applied more widely in elderly patients, too. Here we report the results of all consecutive alloHSCT recipients above the age of 55 years transplanted at our institution between October 1996 and April 2006. Among 89 elderly patients transplanted, 50 patients were in the age group over 55 to 60 years, 31 patients in the cohort over 60 to 65 years, and 8 patients were older than 65 years. 36 patients were female and 53 male. Diagnoses included acute lymphoblastic leukemia (ALL, 10 patients), acute myelogenous leukemia (AML, 32), myelodysplastic syndromes (MDS) or secondary AML (30), chronic myelogenous leukemia (CML, 5), agnogenic myeloid metaplasia (AMM, 3), lymphoma (5), and multiple myeloma (4 patients). Advanced disease was present in 63 patients (71%) at the time of transplant. 85 patients (96%) had a WHO performance score of 0 or 1. Conditioning regimen was myeloablative in 20 patients (22%) and of reduced intensity in 69 patients (78%); in 46 patients (52%) irradiation was part of the conditioning regimen. Stem cell source was peripheral blood in 83 patients (93%) and bone marrow in 6 (7%). 32 patients (36%) received a graft from a related donor and 57 (64%) from an unrelated donor. After a median follow-up of 9 months (range: 1 to 104), 24 patients have since relapsed (27%). Treament related mortality was 27% (24 of 89 patients). 34 patients developed acute graft-versus-host disease (GvHD, 38%) and chronic GvHD was diagnosed in 25 of 71 patients at risk (35%). As of August 1st, 2006, 47 of 89 patients were alive and 41 of 89 in complete remission. Probabilities of overall and disease-free survival at three years were 45 and 32%, respectively. Interestingly, overall and disease-free survival were similar among the three age cohorts. In conclusion, according to our experience, alloHSCT is feasible in elderly patients of appropriate performance status, with acceptable relapse rates and toxicity.
Figure Probability of overall survival in elderly patients after alloHSTC Figure Probability of overall survival in elderly patients after alloHSTC
Long-Term Follow-Up of Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.
Authors: Kuruvilla John , Bao Qikun , Goldberg Mira , Gupta Vikas , Kiss Thomas L. , Lipton Jeffrey H. , Minden Mark D. , Messner Hans A. 
Published: October 2019

Abstract
Introduction
Allogeneic stem cell transplantation (Allo-SCT) remains an option for patients with chronic lymphocytic lymphoma (CLL). Our program employs a strategy using allo-SCT for patients (pts) with high risk disease based on clinical characteristics and prior therapy. We performed a retrospective analysis to examine long-term disease control and treatment toxicity.
Methods
A total of 52 patients (pts) are included who underwent allo-SCT at our institution between Aug 1989 and Dec 2005. Patients were in a chemosensitive remission at the time of SCT. The conditioning regimen consisted of busulfan (1 mg/kg PO q6h X4 days between 1989–200 and 3.2 mg/kg IV daily X 4days subsequently) and cyclophosphamide 60 mg/kg X 2 days. Cyclophosphamide 60 mg/kg X 2 days and TBI 12 Gy was used for unrelated donor SCT. Reduced intensity conditioning (RIC) SCT were typically performed with Fludarabine 50 mg/m2 for 4 days and 2 Gy TBI. GVHD prophylaxis was with cyclosporine A and methotrexate.
Results
There were 34 males and 18 females. The median age at the time of transplant was 51 years (range 26 to 65). Histologic subtype was: CLL and/or small lymphocytic lymphoma (SLL); 48 and T-prolymphocytic leukemia (PLL): 4. The median number of prior chemotherapy regimens was 3 (range 1 – 10) and was unavailable in 16. Prior chemotherapies included: anthracycline-based: 24, prior purine analog: 32, prior platinum-based: 8, prior auto-SCT: 1, prior rituximab: 5. The median time from diagnosis to allo-SCT was 58 months (range 5 – 260). 10 pts underwent RIC SCT. Graft source was: matched sibling (MSD) bone marrow (BM): 18, MSD peripheral blood stem cells (PBSC): 20, Mismatch related (MMRD) bone marrow (BM): 1, MRD PBSC: 4, matched unrelated donor (MUD) BM: 8, MUD PBSC: 1. At 5 years, the overall survival of the entire cohort is 51% (95% confidence intervals: 34 – 68%) with two long-term survivors of 14 and 17 years. Treatment-related mortality (TRM) was 20 of 52 pts (38%). 4 pts have relapsed ((8% of total cohort) and non-relapse mortality was 1 pt (2%). Overall survival by intensity of SCT conditioning regimen was not significant (p=0.3). TRM was similar in pts who received fully myeloablative SCT (40% vs. 20% in RICSCT group, p=0.29).
Conclusions
Acceptable survival post-SCT is possible using an allo-SCT strategy in CLL. However, TRM remains high in this group of heavily pre-treated patients with a median age of over 50 that predominantly received fully myeloablative allo-SCT. Due to small sample size, the potential benefit of reduced TRM with RICSCT cannot be demonstrated. Ideally, allo-SCT should be considered earlier in the course of the disease based on risk stratification utilizing traditional risk factors and modern prognostic factors such as FISH studies and novel markers.
A Comparison of Beam and Yttrium 90 Ibritumomab Tiuxetan (Zevalin®) in Addition to Beam (Z-BEAM) in Older Patients Undergoing Autologous Stem Cell Transplant (ASCT) for B-Cell Lymphomas: Impact of Radioimmunotherapy on Transplant Outcomes.
Authors: Krishnan Amrita Y. , Nademanee Auayporn , Raubitschek Andrew , Fung Henry C. , Molina Arturo , Yamauchi David , Falk Peter M. , Spielberger Ricardo , Palmer Joycelynne , Tsai Ni Chun , Schriber Jeffrey , Forman Stephen J. 
Published: October 2019

Abstract
Background: ASCT is an effective treatment for patients with high risk NHL. However, relapse rates remain high. Attempts at further dose intensification are limited by regimen-related toxicity especially in older patients. Zevalin as a single agent has showed activity in aggressive Non-Hodgkin’s Lymphoma (NHL). We therefore, devised a novel conditioning regimen (Z-BEAM) combining standard dose Zevalin (0.4mci/kg) with high dose BEAM (BCNU 150mg/m2 day-7,-6, cytarabine 800mg/m2 and etoposide 800mg/m2 day-5 to day-2, and melphalan 140mg/m2 day-1).
Herein, we provide an update on the study and also retrospectively compare this new conditioning regimen with conventional high dose BEAM in older patients (age >=50). Between 1995 and 2005, 65 patients (BEAM n=32, Z-BEAM n=33) underwent ASCT utilizing these regimens. Patient selection was similar for Z-BEAM and BEAM. Patients received BEAM prior to the opening of the Z-BEAM protocol and similiarly after the Z-BEAM protocol completed accrual. The groups were well matched for most demographics and disease status. Median age: Z-BEAM - 62 yrs (range 50–78), BEAM - 64 yrs (range 50–77); 1st CR/PR pts comprised 45% in the Z-BEAM arm and 34% in the BEAM, > =1st Relapse 42% vs 50% and induction failure 12% vs 15%. (p=0.7). Median number of prior regimens was 3 in the Z-BEAM group vs 2 in the BEAM arm.(p=0.08) 54 % had bulky disease at diagnosis in the Z-BEAM group vs 41% in the BEAM group (p=0.30).
Results: Two-year OS was 78% for all pts (95%CI, 67–86). Two-year OS/PFS in the Z-BEAM group was 88%(95% CI, 70–95)/72 %(95% CI, 57–83) respectively vs 65% (95%CI, 48–77)/ 67%( 95CI, 50–79) in the BEAM group (Figure1). Analysis by histology showed that in patients with diffuse large B-cell lymphoma (DLBCL), there was a significant difference in OS/PFS of Z-BEAM vs BEAM, 95% vs 48% at 2 yrs (p=.009)/ 88% vs 48% ( p=0.015). The OS/PFS difference of Z-BEAM vs BEAM in patients with mantle cell lymphoma did not reach significance. The toxicity profile and transplant related mortality was similar in both regimens.
Conclusions: Our study suggests that the addition of Zevalin to the BEAM conditioning regimen is feasible and well tolerated in older patients. The favorable outcome of patients treated with Z-BEAM compared with BEAM alone, especially in patients with DLBCL, suggests that prospective study in a randomized trial is warranted.
Overall Survival   ZBEAM versus BEAM Overall Survival   ZBEAM versus BEAM
Autologous Stem-Cell Transplant with a Rituximab Purge and Maintenance vs. Standard Chemotherapy for Mantle Cell Lymphoma: Extended Follow-Up of a Matched Pair Analysis.
Authors: Hicks Lisa , Connors Joseph M. , Mangel Joy , Buckstein Rena , Crump Michael , Leitch Heather , Imrie Kevin , Nagy Tracy , Boudreau Angela , Pennell Nancy , Spaner David , Berinstein Neil 
Published: October 2019

Abstract
Background: We previously reported that 20 patients with newly diagnosed, stage III/IV mantle cell lymphoma (MCL) treated prospectively with an in vivo rituximab purge, autologous stem-cell transplantation (ASCT) and rituximab maintenance experienced superior progression free survival (PFS) compared to 40 matched, historical controls treated with conventional chemotherapy. We now report extended follow-up from this trial.
Methods: Eligible patients were treated with 4–6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by high dose therapy (cyclophosphamide, carmustine and etoposide) and ASCT. Rituximab (375 mg/m2) was given once 5 days prior to stem cell collection (as an in vivo purge), and as two, 4-week maintenance courses 8 and 24 weeks after ASCT. Historical control patients matched for age, stage and gender were randomly selected from a lymphoma database maintained by the British Columbia Cancer Agency. Two control-patients were selected for every trial patient. All control patients were treated with either an anthracycline based-regimen, or a regimen containing fludarabine and cyclophosphamide.
Results: Median follow-up is 5.3 years for the experimental cohort and 10.1 years for the control cohort. In the ASCT cohort, 8 patients have relapsed and 4 patients have died, 2 of progressive disease, 1 of a presumed cardiac event 7 months post-ASCT, and one of hepatitis B reactivation 11 months post-ASCT. Five-year OS and 5-year PFS were superior in MCL patients treated with ASCT+ rituximab compared to matched, historical MCL patients treated with conventional chemotherapy (5y OS 80% vs. 38%, P=0.0017; 5y PFS 72% vs. 19%, P=0.0001). One patient developed myelodysplastic syndrome 5.5 years after ASCT, and one patient was diagnosed with breast cancer 4.8 years after ASCT.
Conclusions: With more than 5 years of follow-up MCL patients treated with ASCT plus rituximab continue to experience significantly improved OS and PFS compared to matched, historical controls.
Overall Survival Overall Survival