bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitoxantrone and Melphalan as Conditioning Regimen for Autologous Stem Cell Transplant for Multiple Myeloma.
Authors: Beaven Anne W. , Comeau Terrance , Sharf Andrew , Moore Dominic T. , Serody Jonathan , Shea Thomas C. , Gabriel Don A. 
Published: October 2019

Abstract
High dose Melphalan (Mel) has demonstrated efficacy in the treatment of multiple myeloma (MM). Mitoxantrone (Mit), in combination with vincristine and prednisone, also has demonstrated activity in MM with the benefit of less cardiac toxicity than other standard regimens. In this trial Mel and Mit were combined as a transplant preparative regimen. Mit was given as a prolonged 6 hour infusion on 2 separate days to increase intracellular drug levels and decrease cardiac toxicity (Kaminer et al. Cancer1990; 65, 2619–2623; Koc et al. Hematol Oncol2004;22:43–53).
PATIENTS: 35 patients with a diagnosis of MM were enrolled between 9/98–6/02. Median age was 59 (range, 38–69); 60% had received ≥ 2 previous regimens (range, 1–6). The median time from diagnosis to transplant was 9 months (95% CI, 8–12 months). 57% had stage III disease and 26% stage II at diagnosis; median Beta-2 microglobulin was 3.6 mg/L (available in only 13 patients). All patients completed therapy with Mit 30mg/m2/day infused over 6 hours on days -6 and -5 and Mel 180mg/m2 on day -1.
RESULTS: The median follow-up for survivors was approximately 45 months (range, 3–84 months). The median times to granulocyte and platelet engraftment were 11 days and 14 days respectively. 2 patients failed to engraft; 1 proceeded to allogeneic transplant, the other died on day 28 secondary to sepsis. The 100-day TRM was 2.9%. The median progression free survival (PFS) was 20 months (95% CI, 13–31) (Figure 1) with a median overall survival (OS) of 57 months (Figure 2). 4 patients are alive and progression free more than 48 months out from transplant. 8/35 (23%) of patients achieved a complete response (CR). Of the 8 patients who had a CR, 7 (20% of total patients) are still alive and progression free with a median follow-up of 39 months after transplant (range, 12 to 80 months). The achievement of a CR was significantly associated with longer PFS but not with OS. The mean CD34 count of infused cells was 4.92 ×106/kg and did not appear to be significantly associated with CR rate, OS, or time to engraftment of platelets or granulocytes. Overall, therapy was well tolerated with a median of 8 days (range, 0–15) of any grade of mucositis and a median of 3 days of fever. The mean LVEF on MUGA was 64% pre-transplant and decreased to 58% post-transplant. 1 patient with diabetes and hypertension developed congestive heart failure after discharge from the hospital but with therapy the LVEF returned to normal.
CONCLUSION: The combination of Mel and infusional Mit is an effective regimen with 23% CR rate despite multiple previous therapies. The median OS of 57 months compares well to other transplant trials and patients who achieved a CR demonstrated better long-term PFS.
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Transplantation without Growth Factor. Engraftment Kinetics Following Stem Cell Transplantation for Primary Systemic Amyloidosis.
Authors: Gertz Morie Abraham , Lacy Martha Q. , Dispenzieri Angela , Hayman Suzanne R. , Kumar Shaji K. , Gastineau Dennis A. 
Published: October 2019

INTRODUCTION
The use of growth factors filgrastim and sargramostim are associated with often dramatic degrees of fluid retention in patients with amyloidosis who have coexistent cardiac involvement or nephrotic syndrome. Significant degrees of fluid retention can complicate the post transplant management of patients with AL receiving high dose chemotherapy. We report outcomes in a cohort of amyloidosis patients who received no growth factor support post transplant.
PATIENTS AND METHODS
283 consecutive patients seen for stem cell transplant are included in this cohort. In order to be considered evaluable for engraftment the patient must have survived for 30 days or was excluded from analysis. All patients had biopsy verified AL. Patients also had to have visceral organ dysfunction in order to be eligible for stem cell transplant with a minimum of one visceral organ involved.
RESULTS
Among 283 patients transplanted, 244 were evaluable for engraftment. There were 145 men (59%). Renal involvement was present in 163 (67%), cardiac involvement by echocardiography in 47%, hepatic involvement in 16%, and peripheral nerve involvement in 11%. The median age was 56.6 years (range 33–73). The median time from diagnosis of amyloidosis to stem cell transplantation was 4.2 months. A neutrophil count of 500/uL was achieved in 50%, 75%, and 90% of the total group at 14, 16, and 22 days respectively (figure 1). A platelet count of 20,000/uL was achieved in 50%, 75%, and 90% of patients at 14, 19, and 28 days respectively (figure 2). A platelet count of 50,000/uL was achieved in 50%, 75%, and 90% of patients at 18, 28, and 52 days respectively. The median time spent in the hospital for the entire cohort 9 days. 46 of the patients (19%) completed the entire procedure as an outpatient. 75% of patients were discharged within 18 days and 90% were discharged within 32 days. 137 patients were blood culture negative throughout the entire procedure (56%). A blood culture was positive in the remaining 107 patients. 68 of these 107 contained a culture for Staph. coagulase negative. 39 (16%) had bacteremia associated with other organisms.
CONCLUSION
Transplantation of patients with amyloidosis without using growth factor is feasible. The median time to achieve neutrophil and platelet counts of 500 and 20,000/uL respectively is 14 days. It is reasonable to withhold growth factor from AL patients undergoing stem cell transplantation.
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Clonal Evolution in Chronic Lymphocytic Leukemia: Acquisition of High-Risk Genomic Aberrations Associated with Unmutated VH, Resistance to Therapy, and Short Survival.
Authors: Stilgenbauer Stephan , Sander Sandrine , Bullinger Lars , Benner Axel , Leupolt Elke , Winkler Dirk , Kröber Alexander , Kienle Dirk , Lichter Peter , Döhner Hartmut 
Published: October 2019

Abstract
Genomic aberrations were analyzed by fluorescence in situ hybridization (FISH) at various time points during the disease course of 64 patients with chronic lymphocytic leukemia (CLL) from a single institution. After a median time of 42 (23–73) months, 11 of the 64 (17%) patients acquired the following additional aberrations: del(17p13) (n=4), del(6q21) (n=3), del(11q23) (n=2), +(8q24) (n=1), and evolution from monoallelic to biallelic del(13q14) (n=3). The baseline clinical characteristics of the patients with and without clonal evolution were not significantly different. Remarkably, clonal evolution occurred exclusively among cases with unmutated VH status (Figure 1). The group with clonal evolution showed a higher rate of progression in stage (82% vs. 28%), a greater need for treatment (100% vs. 62%), and a higher death rate (67% vs. 28%). The median survival time after the occurrence of clonal evolution was 22 months. Expansion of the clone with del(17p13) was observed in all patients during chemotherapy (chlorambucil n=4, fludarabine n=3, FC n=2, rituximab n=1) indicating in-vivo resistance to treatment (Figure 2). In multivariate analysis, clonal evolution was identified as independent adverse factor with regard to overall survival.
Figure 1 Figure 1. Figure 2 Figure 2.
Outcome of Diffuse Alveolar Hemorrhage in Hematopoietic Stem Cell Transplant Recipients.
Authors: Gupta Sachin , Jain Amit , Gupta Aditya , Warneke Carla L. , Giralt Sergio , Eapen Georgie A. 
Published: October 2019

Abstract
Background: Hematopoietic Stem Cell Transplantation (HSCT) is being widely used as an adjunct to conventional chemoradiotherapy for many hematologic and solid malignancies and some non-malignant hematologic conditions. Diffuse Alveolar Hemorrhage (DAH) is seen in 1 to 19% of HSCT recipients who undergo bronchoscopy. Though, the reported mortality of DAH is 70–100%, the outcomes are changing with advances in preconditioning, stem cell transplantation and intensive care.
Objectives: To study the outcomes of DAH and factors associated with adverse outcomes in HSCT recipients at M.D. Anderson Cancer Center.
Methods: A retrospective review of all adult patients who underwent bronchoscopy after HSCT between January 1, 2002 and December 31, 2004 for a presumptive diagnosis of DAH. Outcome measures were recorded and analyzed over the six months following bronchoscopy. Univariate and multivariate Cox proportional hazards regression models were used to investigate prognostic value of various clinical factors.
Results: Bronchoscopy with BAL was performed in 223 patients for a clinical suspicion of DAH. Blood was seen on bronchoscopy in 87 (39%) patients. All patients received high dose steroids and other supportive care. Fifty-three (61%) met the standard criteria for diagnosis of DAH while 34 had an organism isolated on BAL. Of these 53 patients, 66% were alive at 30 days, and 45% at 6 months. Overall, 42% were alive at the end of follow-up period. Respiratory failure was recorded as the cause of death in 52%. Outcomes were significantly worse in the 34 patients with an organism in BAL. Significant associations existed between poorer overall survival and isolation of an organism in BAL (HR = 1.99, 95% CI: 1.38, 2.87), renal dysfunction (HR = 2.35, 95% CI: 1.60, 3.46), and neutropenia (HR = 2.77, 95% CI: 1.91, 4.01).
Conclusion: The survival of patients with DAH at our center is better then that reported in literature. Isolation of an organism in BAL, renal dysfunction, and neutropenia are associated with increased risk of death among patients undergoing bronchoscopy after HSCT.
Prevention of Oral Mucositis with Palifermin in Patients Treated with High-Dose Chemotherapy and Autologous Stem Cell Transplantation. A Single Center Experience.
Authors: Luthi Francois , Berwert Lorenzo , Frossard Valérie , Marchetti Oscar , Rosselet Anne , Duchosal Michel , Ketterer Nicolas 
Published: October 2019

Abstract
It was demonstrated in a placebo controlled randomized study that Palifemin decrease the severity of oral mucositis in patients (pts) treated with total body irradiation (TBI), high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). The benefit of this treatment in pts who are not receiving TBI-containing conditioning regimen is still unclear. We evaluated prospectively the effect of Palifermin on mucositis prevention in 34 consecutive pts treated with HDCT and ASCT compared to an historical group of pts who did not receive Palifermin.
Between 03/2005 and 05/2006, 34 pts (Group A) treated with Melphalan 200 (n=15) or BEAM (n=19) gave informed consent and received 6 injections of 0.06 mg/kg of Palifermin (3 days (d.) before HDCT and 3 d. following ASCT). Four were excluded from efficacy analysis, 2 of them due to Melphalan dose reduction and 2 due to early discontinuation of Palifermin. They were compared to 77 pts (Group B) treated with Melphalan 200 (n=43) or BEAM (n=34) from 2003 to 2005. WHO grading was used for toxicity assessment.
The median age was 55 years in group A (Range 28–67) and 54 years in group B (Range 19–66). The median count of CD34 cells/kg infused was 4.2 millions (Range 1.96–23.9) in group A and 3.85 millions (Range 1.8–16.2) in group B. The median time for engraftment was the same in both groups and was respectively 11 d. for neutrophils (Range 8–12) and 11 d. for platelets (Range 8–13) in group A, 11 d. for neutrophils (Range 8–13) and 11 d. for platelets (Range 8–18) in group B. Severe oral mucositis (Grade 3 and 4) was lower in group A (17%) than in group B (44%). The incidence of grade 2 or more digestive mucositis was similar in the 2 groups (66% vs.60%) as well as the total opioid use (43% vs 57%). All patients but one in the group B developed fever. Fever of unknown origin were more frequent in group A due to less fever attributed to grade 3 or 4 mucositis.In group A, all but 3 pts developed toxicities. Grade 3 or 4 toxicities consisted in erythematous rash in 15 pts (44%), generalized oedema in 2 and odynophagia in 1. Grade 1 or 2 toxicities were pruritis (24%), rash (32%), localized oedema (26%) and buccal discomfort (41%). 1 pt died at d.12 from an hemophagocytic syndroma and onother at d.90 from a rapidly progressive colorectal cancer.
We conclude that the use of Palifermin reduced the incidence of grade 3 or 4 mucositis in our group of pts treated without TBI, but did not decrease either digestive mucositis or the use of morphinic. The benefit of Palifermin on mucositis prevention has still to be balanced again the risk of discomfort and toxicities of this drug. Large randomized studies are still needed before recommending the systematic administration of Palifermin to pts receiving Melphalan 200 or BEAM as conditioning regimen before ASCT.
No Evidence for Increased Transplant Related Complications in Ph+ Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia with Prior Treatment with Dasatinib.
Authors: Leiba Merav , Shimoni Avichai , Guilhot Francois , Martineau Geraldine , Renaud Marc , Francois Sylvie , Hardan Izhar , Nagler Arnon 
Published: October 2019

Abstract
Stem cell transplantation (SCT) is frequently used as salvage or curative therapy in patients (pts) with advanced chronic myelogenous leukemia (CML) or Ph+ acute lymphoblastic leukemia(ALL) who were previously treated with Imatinib. While one study showed higher incidence of GVHD, VOD and TRM, most studies have demonstrated that Imatinib therapy prior to SCT does not adversely affect transplantation outcome. Dasatinib is a novel dual SRC/ABL kinase inhibitor currently being used in pts with Imatinib-resistant advanced CML or relapsed/efractory Ph+ ALL. Most of these pts will eventually undergo SCT, raising the question of whether Dasatinib therapy may adversely affect transplantation outcome. We report eight pts: CML -6 (CP1-4, low sokal score -3, high sokal score -1, CP2-1, AP-1) and Ph+ ALL -2 who received Dasatinib prior to alloSCT (n=7) or autoSCT (n=1). Donors were matched siblings -4, matched unrelated -2 or mismatch related donor (haploSCT) -1. Five were male and 3 female with a median age of 46.5 (16–56) years. First line therapies included Hydroxyurea or Interferon followed by Imatinib for the CP CML pts and chemotherapy followed by Imatinib for the advanced CML and Ph+ ALL pts. All pts subsequently received Dasatinib 70mg × 2/day due to resistance to Imatinib, resulting in complete hematological response in all, as well as complete (n=5) or partial cytogenetic response (CyR) (n=2) prior to SCT. One pt did not achieve CyR prior to SCT. The pts were conditioned with either a myeloablative protocol (n=5) or a reduced intensity protocol (n=3). GVHD prophylaxis consisted of CSA and MTX (n=6) or complete T-cell depletion (n=1). Pts received a mobilized peripheral blood stem cell graft with 11.4–19.8 × 106 CD34+ cells/kg. The pt who underwent autoSCT was successfully mobilized (2 apheresis cycles yielding 5.7 × 106 CD34+/kg). Dasatinib was stopped 6 days before mobilization. All pts successfully engrafted reaching ANC > 0.5×109/L on day +14 (11–21) and PLT >20×109/L on day +12.5 (11–17). Chimerism was 99.4 – 100%. Transplant related toxicities were minimal. Only one pt developed severe mucositis. No pt developed hyperbilirubinemia or VOD. There was no increased risk of infections. Acute GVHD (Gr II) was observed in only 1 pt, while 2 developed extensive chronic GVHD (1 after stopping immunosuppression). With a median follow-up of 8.5 (2–13) months, six pts are alive, 5 in CR, while 2 died of disease progression. We may conclude that in pts undergoing SCT following Dasatinib there is no evidence that Dasatinib adversely affect post SCT outcome, as no increased transplant related organ toxicities, non-engraftment, GVHD or infections were observed. Larger studies are obviously indicated to confirm our preliminary results.
Baseline Inflammatory Cytokines Predicted Rapid Increase in Symptom Severity to Nadir of Allogeneic BMT.
Authors: Wang Xin Shelley , Williams Loretta , Shi Qiuling , Giralt Sergio A. , Cleeland Charles S. 
Published: October 2019

Abstract
Patients who undergo allogeneic BMT experience a rapid increase in multiple symptoms, including pain, fatigue, poor appetite, drowsiness, dry mouth, and disturbed sleep, from pre-BMT to nadir of white blood cell count. The objective of this study was to prospectively evaluate baseline levels of serum inflammatory cytokines and other factors related to symptom development from pre-BMT to nadir.
Methods: Repeated multiple-symptom assessments with the M. D. Anderson Symptom Inventory (MDASI) were completed for 30 patients with AML/MDS at day of hospital admission (baseline), day of conditioning, day of BMT, day of nadir, and day 11 of BMT. A panel of serum inflammatory cytokines (IL-1ra, IL-6, IL-8, IL-10, IL-12, TNF-a) was assayed at baseline, conditioning, day of BMT, day after BMT, and at nadir.
Results: Patients self reported multiple symptoms that peaked 3 days after nadir. We adjusted for potential confounding factors, including age, sex, race, disease status pre-BMT, infusion dose of CD34+, and conditioning regimen, that could have affected symptom outcomes in the mixed effect models for symptom severity. Race was the only significant factor affecting the severity of the baseline symptom cluster (pain, fatigue, poor appetite, disturbed sleep, drowsiness, and dry mouth) and the change in symptom severity from baseline to peak (P<.0001). We were interested to know if baseline cytokines had any role in symptom development. Of the panel of cytokines tested, IL-6, IL-8, and IL-1b were significant predictors of the severity of symptom cluster from baseline to peak (estimated values from mixed modeling were 1.196, −3.707, and 6.055, all P<.05).
Conclusion: These results provide the first evidence of the role of baseline serum pro-inflammatory cytokines in symptom development from pre-BMT to symptom peak around nadir in patients with AML/MDS who have undergone allogeneic BMT.
A Randomized Trial of Bone Marrow (BM) Versus Peripheral Blood (PB) Allogeneic Hemopoietic Stem Cell Transplants (HSCT) in Patients with Myeloproliferative Disorders.
Authors: Bacigalupo Andrea , van Lint Maria Teresa , Olivieri Attilio , Casini Marco , Angelucci Emanuele , Narni Franco , Selleri Carmine , Di Bartolomeo Paolo , Ciceri Fabio , Fanin Renato 
Published: October 2019

Abstract
Background. Reduced intensity conditioning (RIC) regimens have been widely used over the past years with the aim of reducing transplant related mortality (TRM) of allogeneic hemopoietic stem cells transplants (HSCT). The preferred source is peripheral blood (PB) cells, although this source has not been prospectively compared with bone marrow (BM) iun the setting of RIC transplants.
Aim of the study. To compare BM and PB allogeneic transplants following a RIC regimen in patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML) or idiopathic myelofibrosis (IM).
Methods and patients. This is a prospective multicenter randomized trial: eligible were patients with AML, CML and IM, aged 45–60, with an HLA identical sibling, Conditioning regimen was thiotepa 5 mg/kgx2 and cyclophopshamide 50 mg/kgx2. Graft versus host disease (GvHD) prophylaxis was low dose cyclosporin and low dose methotrexate. Patients were randomized to receive unmanipulated BM (n=36) or unmanipulated PB (n=35), after stratification for disease phase (1st remission, n=47) or advanced disease (n=24). Median age was 51 in both groups and follow up of surviving patients 760 and 756 days respectively.
Results. Engraftment was achieved in all but one patient who has autologous reconstitution. Acute GvHD grade III–IV accurred in 0% vs 12% of BM vs PB patients (p=0.03) and extensive chronic GvHD in 13% vs 37% respectively (p=0.03).
Cumulative incidence (CI) of TRM at 5 years is 6% for BM and 9% for PB (p=0.6). Relapse of the original disease occurred in 61% vs 29% of BM and PB patients (p=0.007) and the CI of relapse related death (RRD) is 39% vs 19% respectively (p=0.07). Actuarial 5 year survival is 47% in BM vs 68% in PB paitents (p=0.3). A COX proportional step down analysis shows chronic GvHD to be a significant favourable factor for RRD and survival. Conclusions. In patients receiving a RIC allogeneic graftTRM is low and comparable in BM and PB transplanst;acute and chronic GvHD is more frequent in PB transplants,relapse is significantly decreased in PB transplants and RRD is also lower,there is a non significant survival advantage for PB patients andthe occurrence of chronic GvHD protects against relapse and favourably influences long term survival.
Phenotypic and Functional Analysis of T-Cells Mobilized in HLA-Matched Sibling Donors Following Treatment with the Chemokine Antagonist AMD3100.
Authors: Rettig Michael , Devine Steven M. , Ritchey Julie , DiPersio John F. 
Published: October 2019

Abstract
We are currently evaluating a novel method for the procurement of peripheral blood stem cells from HLA matched sibling donors using a direct antagonist of the CXCR4/SDF-1 interaction called AMD3100 (A). Donors receive a single subcutaneous injection of A and then undergo a 20 liter leukapheresis (LP) four hours later. The LP product is then cryopreserved and subsequently transplanted following ablative conditioning. To date, we have performed 15 transplants with allografts collected following A alone. In comparison to allografts collected following five days of G-CSF, A mobilized allografts contain approximately 50% less CD34+ cells but 2–3 times more CD3+ cells. Nevertheless, the kinetics of neutrophil and platelet engraftment have been virtually identical to that observed following G-mobilized allografts and grades 2–4 acute GVHD has been observed in only 20% of recipients. We sought to analyze the functional and phenotypic properties of T cells collected following A alone to understand the relatively low rates of acute GVHD despite the transplantation of higher T-cell doses. In 3 donors, extensive T cell phenotyping was performed on donor peripheral blood prior to A, 6 hours following A, and also on the LP product collected after A. Specifically, we were seeking to determine whether any alteration in CD4+ or CD8+ subsets had occurred. We analyzed T-cell subsets using well described markers for central memory, effector memory, naïve, and effector memory RA phenotypes. We also assessed expression of CD62L, CD127, CCR7, and SLAM family members (CD48, CD150, and CD244) on both CD4+ and CD8+ cells. The activation status on CD4 and CD8 cells was assessed using markers for CD25, CD30, and CD69. Finally we assessed for quantitative changes in the mobilization of regulatory T cells by assaying the proportion of CD4+CD25+FoxP3+ cells mobilized following A. In none of these analyses could we detect any significant alteration in the relative ratios of CD4 or CD8 subsets mobilized by A. Finally, the functional capacity of purified CD3+ cells collected following A was assessed using a NOD/SCID xenogeneic GVHD model we have recently developed. In that model, survival of mice transplanted with A mobilized T-cells was similar to that observed with untreated T cells, suggesting that A mobilized T cells retain their GVHD-inducing capacity. In summary, these preliminary data suggest that AMD3100 induces a “pan-mobilization” of T cell subsets without any apparent skewing toward a particular subset. These studies are in contrast to others suggesting subtle phenotypic and functional changes in donor T cells after mobilization with G-CSF. Further studies evaluating A mobilized allografts are ongoing.