scholarly journals Haploidentical stem cell transplant with post-transplantation cyclophosphamide and mini-dose methotrexate in children

2020 ◽  
Vol 13 (4) ◽  
pp. 208-213 ◽  
Author(s):  
Diego Medina ◽  
Mayra Estacio ◽  
Maria Rosales ◽  
Eliana Manzi
Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 633 ◽  
Author(s):  
Antonin Bal ◽  
Clémentine Sarkozy ◽  
Laurence Josset ◽  
Valérie Cheynet ◽  
Guy Oriol ◽  
...  

Over recent years, there has been increasing interest in the use of the anelloviruses, the major component of the human virome, for the prediction of post-transplant complications such as severe infections. Due to an important diversity, the comprehensive characterization of this viral family over time has been poorly studied. To overcome this challenge, we used a metagenomic next-generation sequencing (mNGS) approach with the aim of determining the individual anellovirus profile of autologous stem cell transplant (ASCT) patients. We conducted a prospective pilot study on a homogeneous patient cohort regarding the chemotherapy regimens that included 10 ASCT recipients. A validated viral mNGS workflow was used on 108 plasma samples collected at 11 time points from diagnosis to 90 days post-transplantation. A complex interindividual variability in terms of abundance and composition was noticed. In particular, a strong sex effect was found and confirmed using quantitative PCR targeting torque teno virus, the most abundant anellovirus. Interestingly, an important turnover in the anellovirus composition was observed during the course of the disease revealing a strong intra-individual variability. Although more studies are needed to better understand anellovirus dynamics, these findings are of prime importance for their future use as biomarkers of immune competence.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-5
Author(s):  
Joyce Philip ◽  
Shivani Sharma ◽  
Vijayalakshmi Donthireddy

Background: Treatment for primary CNS lymphoma involves a methotrexate-based induction therapy followed by consolidation. The optimal consolidation treatment after induction with a high dose Methotrexate (HD-MTX), Rituximab and Temozolomide regimen has not been fully established. The CALGB 50202 regimen using Etoposide and Cytarabine consolidation was associated with significant toxicity. We sought to review the results of alternative consolidation regimens and evaluate the progression free survival and overall survival. Methods: A retrospective cohort study was conducted to evaluate the efficacy of alternative consolidation regimens such as autologous stem cell transplant and HDMTx alone. Patients diagnosed with primary CNS lymphoma between November 2012 and March 2019 were identified. All patients received the same induction chemotherapy based on the CALGB 50202 protocol. Data was collected for baseline characteristics, progression free survival and overall survival. Results: 38 patients had a diagnosis of primary CNS lymphoma. 15 patients received treatment as per the CALBG 50202 induction protocol with high dose Methotrexate, Rituximab and Temozolomide. Of the 15 patients, 11 patients (69%) achieved a complete remission (CR) after induction therapy. 7 patients received an autologous stem cell transplant for consolidation, 5 patients received HD-MTX alone for consolidation and one patient was placed on Lenalidomide maintenance. 2 patients did not receive any consolidation therapy due to progressive disease and/or death. At a median follow up of 2.7 years for the entire cohort, median PFS was 31.7+ months and median OS was 32.5+ months. At a median follow up of 2.7 years for patients who were consolidated with an autologous stem cell transplant, median PFS and median OS was 27.2+ and 32.5+ months respectively. At a median follow up of 5.5 years for patients who were consolidated with treatments other than transplant, median PFS and OS was 65.6+ months. There were no deaths attributed to treatment related toxicity. To date, 4 patients of the entire cohort have died, with a median survival time among surviving patients of 3.6 years (range, 0.68-7.05 years). There were no deaths attributed to treatment related toxicity. Conclusion: Patients with primary CNS lymphoma who received induction therapy as per CALGB 50202 regimen and received alternative consolidation therapies with either autologous stem cell transplant or HD-MTX based consolidation achieved prolonged PFS and OS comparable if not superior to the Etoposide and Cytarabine consolidation. Results of the ongoing CALGB 51101 trial will determine the utility of EA consolidation. Disclosures No relevant conflicts of interest to declare.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6524-6524 ◽  
Author(s):  
L. C. Michaelis ◽  
D. Sher ◽  
M. Myers ◽  
M. Siddiqui ◽  
D. Collins-Jones ◽  
...  

6524 Background: Expression of WT-1, a zinc-finger transcription factor, is elevated at diagnosis in many kinds of leukemia. The prognostic significance of the WT-1 transcript level before and after stem cell transplant is controversial. We performed real-time quantitative PCR (RQ-PCR) on samples from pts with leukemia and MDS undergoing allo stem-cell transplant (SCT) to determine if WT-1 expression correlates with survival (OS) and/or disease-free survival (DFS). Methods: Pts were conditioned with fludarabine, melphalan and alemtuzumab. cDNA was synthesized for RQ-PCR, which was performed on bone marrow (BM) and peripheral blood (PB) samples drawn prior to transplant admission and at day 28 (D28) post transplantation. All samples were analyzed using LightCycler technology and reported as a normalized ratio of WT-1 copy number to ABL copy number. Results: Data on 48 patients who underwent allo SCT are reported here. During a median follow up of 17 months, 24 patients died and the OS rate at one year was 52%. The DFS rate at one year was 34%. There was a statistically significant association between pretransplant WT-1 levels measured in PB and OS, with increase in risk of death by 36% for every 10 fold increase in WT-1 levels (p=0.048). Pretransplant WT-1 levels in both PB and BM also predicted DFS: the risk of relapse or death was increased by 44% (PB) and 71% (BM) for every 10 fold increase in WT-1 levels (p=0.012; p=0.048). However, after controlling for disease status at transplantation using a Cox model, pretransplant WT-1 levels were no longer a significant predictor because these levels were highly correlated with disease status at transplantation. We did not find any significant correlation between WT-1 levels 28 days post-transplantation and outcome. Conclusions: Our preliminary results differ from several published studies demonstrating prognostic significance of WT-1 RQ-PCR after allo SCT. Although elevated WT-1 levels prior to transplantation correlate with higher risk of post-transplant relapse and death from any cause, these preliminary data fail to establish an independent prognostic role for WT-1 RQ-PCR in the setting of reduced intensity allo SCT. Analysis of additional post-transplant time points is proceeding. No significant financial relationships to disclose.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S130-S131
Author(s):  
Anita R Modi ◽  
Lisa A Rybicki ◽  
Navneet Majhail ◽  
Sherif B Mossad

Abstract Background Infections are the most common cause of non-relapse mortality in adult allogeneic stem cell transplant (allo SCT) recipients. Acute gastrointestinal graft-vs.-host disease (GI GVHD) often leads to friable mucosa and interventions increasing infectious risk. We describe the relationships between increasing grades of acute GI GVHD and incidence of bloodstream infections (BSI) at our institution. Methods We reviewed 441 adults who underwent allo SCT from 2011 to 2017 and were diagnosed with GI GVHD, non-GI GVHD, or no GVHD based on the Modified Glucksberg Scale within the first 100 days of transplant. The maximum grades of GI GVHD and non-GI GVHD were used in the analysis. A BSI episode constituted a blood culture positive for bacteria or fungi and antibiotic treatment. The incidence of BSI within the first 180 days of transplantation was estimated with the cumulative incidence method. Results Overall BSI incidence by day 180 was 32%; Gram-negative bacilli were the predominant organisms. Adjusting for grade of non-GI GVHD, patients with acute grade 4 GI GVHD had higher risk of BSI as compared with patients with no GI GVHD (HR 3.02, P < 0.001), while those with grade 3 GI GVHD had similar risk (HR 1.01, P = 0.98). Patients with grade 1 or 2 GI GVHD demonstrated lower BSI risk compared with those with no GI GVHD (HR 0.48, P = 0.015; HR 0.44, P = 0.08, respectively). Results were similar after adjusting for patient- and transplant-related risk factors for BSI. Grade of GI GVHD had no association with non-BSI risk. Patients who developed BSI or non-BSI had significantly higher overall mortality risk compared with those without infectious complications (HR 2.52, P < 0.001 for BSI; HR 1.60, P = 0.001 for non-BSI). Conclusion Acute grade 4 GI GVHD may reliably indicate higher BSI and overall mortality risk in this population. Understanding the relationships between acute GI GVHD and BSI can guide future treatment strategies for adult allo SCT recipients. Disclosures All authors: No reported disclosures.


2013 ◽  
Vol 6 (1) ◽  
pp. e2014008 ◽  
Author(s):  
Poorvi Chordia ◽  
Pranatharthi H Chandrasekar

Reactivation of human herpes virus-6 (HHV-6) after stem cell transplantation occurs frequently. It is associated with clinical manifestations varying from nonspecific symptoms such as fevers or rash, to severe life threatening complications including post-transplantation limbic encephalitis. We report a case of severe HHV-6 encephalitis with viremia in an allogeneic peripheral stem cell transplant recipient who presented with status epilepticus unresponsive to antiepileptic therapy.  With intravenous ganciclovir and supportive care, the patient’s condition improved. Awareness of HHV-6 infection in stem cell transplant recipients may help with early diagnosis and improved outcome.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4959-4959
Author(s):  
Georgio Medawar ◽  
Audrik Perez Rodriguez ◽  
Caroline Cerio ◽  
Todd F. Roberts ◽  
Kapil Meleveedu

Abstract Background ASCO clinical guidelines recommends administration of WBC growth factors after autologous stem cell transplant (ASCT) to reduce the duration of severe neutropenia (Smith TJ et al., Recommendations for the use of WBC growth factors: American society of clinical oncology clinical practice guideline update. J Clin Oncol, 33(28):3199-3212, 2015). But there is conflicting data regarding the optimal timing of granulocyte colony stimulating factor (G-CSF) initiation post-transplantation and a lack of recent cost effectiveness analysis. Based on single center studies showing similar results between an early approach and a delayed one, we changed our institutional standard to a delayed strategy since June 2020. Methods We retrospectively compared the outcomes of adult multiple myeloma ASCT patients who received G-CSF either on day 2 (early) or day 5 (late) at Roger Williams Medical Center. Sixteen consecutive patients received day 2 G-CSF between July 2018 and June 2020 (D+2 cohort) while seven received day 5 since implementing the change in June 2020 (D+5 cohort). The doses of G-CSF given were 300 mcg, 480 mcg, 600 mcg or 960 mcg. One-way factorial ANOVA and Fit Y by X was used for comparison of variables. Descriptive statistics were used where appropriate. Results Baseline characteristics were comparable between the D+2 and D+5 cohorts (median age 62 vs 63 years, median CD34+cells 4.01 vs 4.54 x10 6/kg respectively). The median number of prior treatments, conditioning intensity, disease status at transplant and G-CSF doses were similar in both cohorts. Median ANC at G-CSF initiation was different (3300 in D+2 vs 100 in D+5). The median follow-up for survivors was 215 days for D+5 cohort (range: 135-404 days) and 699 days for D+2 cohort (range: 418-923 days). The results are summarized in table 1. For the primary outcome, median time to neutrophil engraftment was 13 days versus 10 days in the early and late cohorts, respectively (p=0.07). Median days from administration of GCSF to hospital discharge was noted to be shorter in the late cohort (13 vs 17.5 days, p=0.05). There was no statistically significant difference in the incidence of febrile neutropenia or transfusion requirements with late initiation of G-CSF. While engraftment syndrome and duration of antibiotics were noted to be more in the early cohort, these were not statistically significant. Median length of hospital stay was a day and half shorter in the late cohort. 6-month OS favored the D+5 cohort (p=0.03); this was likely due to transplant related deaths in early cohort. The average cost saving per patient by implementing the late strategy was 887.4 $. Conclusions Late initiation of G-CSF following autologous ASCT in patients with multiple myeloma was associated with a shorter time to neutrophil engraftment and length of stay post transplantation with no difference in overall outcomes. Cost benefit analysis favors delaying initiation of GCSF for autologous SCT at our center. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


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