scholarly journals Outcomes of Therapy Related Acute Lymphoblastic Leukemia in Adults after Allogeneic Stem Cell Transplantation - Twenty-Year Experience from a Tertiary Care Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5717-5717
Author(s):  
RAM V Nampoothiri ◽  
Arjun Law ◽  
Wilson Lam ◽  
Zeyad Al-Shaibani ◽  
David Loach ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Cox Regression Analysis ◽  
Gvhd Prophylaxis ◽  
One Year ◽  
Prior Malignancy ◽  
Related Mortality

Introduction Therapy related acute leukemias are late complications of treatment with mutagenic agents for both malignant and non-malignant disorders. The prevalence of therapy induced Acute lymphoblastic leukemia(t-ALL) is thought to be much less than that of t-AML/MDS, with our institute reporting a 6.9% prevalence of t-ALL among all patients of adult ALL. There is limited data on role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in t-ALL. Recent reports suggested comparable outcomes with de-novo ALL after allo-HSCT. We aim to report our 20-year experience of allo-HSCT in t-ALL. Patients and Methods We retrospectively reviewed all cases of t-ALL who underwent allo-HSCT at our centre from October 1998 to July 2019. Patients were analysed and compared for demographic features, prior malignancy and its treatment, latent period before ALL, clinical, cytogenetic and molecular characteristics of ALL, induction and consolidation treatment received, transplant details including donor details, conditioning regimens, GVHD prophylaxis as well as post-transplant complications (including transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations), relapse rate, relapse free survival (RFS) and overall survival (OS). Predictors of survival were calculated by Cox-Regression Analysis. Results A total of 18 patients underwent allo-HSCT for t-ALL. M:F ratio was 1:1. Median age at allo-HSCT was 44 years (range 20-70 years). Baseline characteristics, prior malignancy and treatment received are summarized in Table 1. Median latent period from prior malignancy to diagnosis of ALL was 44.8 months (range 6-157 months). Complex cytogenetics was present in 16.7% patients (n=3) while 11q23 rearrangement (KMT2A-MLL) and t(9;22) rearrangement was seen in 33.3% (n=6) and 22.2% (n=4) patients respectively. Median time to allo-HSCT from diagnosis of t-ALL was 5 months. Stem cell donors were matched related, matched unrelated and haplo-identical in 27.8% (n=5), 55.6% (n=10), and 16.7% (n=3) patients, respectively. Conditioning regimen was myeloablative in 44.4% (n=8) patients and reduced intensity in 55.6% (n=10) patients. GVHD Prophylaxis used was ATG-CSA-PTCy in 50% (n=9) patients, CSA/MMF in 22.2% (n=4) patients, and other regimens in 27.8% (n=5) patients. Post HSCT CMV and EBV virus reactivation occurred in- 33.3% (n=6) and 47.1% (n=8) patients, respectively. Acute GVHD (any grade) occurred in 70.6% (n = 12) while chronic GVHD (any grade) occurred in 31.3% (n=5) patients. Transplant related mortality (Death before day 100) occurred in 27.8% (n=5) patients. Four (22.2%) patients relapsed. Median RFS was 4 months (Range 0.5-194 months) while median OS was 5.88 months (Range 0.5-194 months) (Figure 1a&b). One patient (5.5%) had relapse of their primary malignancy (CA Breast) 12 years after allo-HSCT. One year RFS and OS for all patients (excluding patients who have not completed one year of followup after HSCT but have not relapsed or died) was 43.8% and 46.7% respectively. None of the basic disease characteristics, treatment characteristics, or transplant or post-transplant parameters including donor type, conditioning received, GVHD prophylaxis used, occurrence of Acute or chronic GVHD etc. were significantly predictive of OS and RFS on Cox-Regression analysis, though the analysis is limited by the small sample size. Conclusions Therapy related ALL is an uncommon but increasingly recognized disease entity. Our outcomes of Allogeneic HSCT in t-ALL were comparable to that in de novo ALL as per previously reported literature. Multicenter studies on t-ALL with more patients and longer follow up duration may provide us with predictive factors of relapse and survival post allogeneic HSCT. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.

Age-Adjusted Recipient Pre-Transplant Telomere Length and Treatment Related Mortality After Hematopoietic Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 490-490
Author(s):  
Régis Peffault de Latour ◽  
Rodrigo T. Calado ◽  
Marc Busson ◽  
Jeffrey Abrams ◽  
Marie Robin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Telomere Length ◽  
Hematopoietic Stem Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Control Group ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Related Mortality

Abstract Abstract 490 Telomeres are highly conserved protective terminal chromosomal structures consisting of hundreds of repeated TTAGGG hexamers and associated shelterin proteins. Telomeres shorten with every cell cycle, and telomere attrition has a fundamental role in cell senescence. Telomeres of leukocytes are shorter in transplant recipients than in their donors. Dyskeratosis congenita, a congenital aplastic anemia caused by mutations in the telomerase complex genes, is associated with treatment related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). We hypothesized that age-adjusted pre-transplant telomere length might generally predict TRM after HSCT. Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donor after myeloablative conditioning regimen (including TBI in 57 patients), mainly for hematological malignancies (n= 153) in our center. The stem cell source was bone marrow (BM) in 128 cases and peripheral blood (PB) in 50 cases. Median age at transplant was 32 years (range 3–65). Graft-versus-host disease (GvHD) prophylaxis mostly consisted of cyclosporine and methotrexate (n=149, 84%). Before HSCT, blood lymphocytes were obtained from each of the donor-recipient pair. Telomere length was assessed by real time quantitative PCR. We first determined the normal age distribution of telomere length using a group of 173 healthy French hematopoietic stem cell donors (f=-0.00833*age+1.522) as a control group. We then calculated the pre-transplant recipient age-adjusted telomere length in comparison to controls. After age adjustment, we categorized the population in quartiles (shortest telomeres for quartile 1) and analyzed the outcome post HSCT using competing risk in univariate and multivariate analyses (Fine and Gray). The mean telomere length in transplant recipients (1.05) was shorter than in the control group (1.23, p= 0.0001). After age-adjustment, patients' distribution was similar among all four quartiles except for disease severity (more high risk disease was present among patients with the shortest telomeres). The median follow-up was 51 months (range, 1 – 121 months). All patients engrafted. The median time to achieve absolute neutrophils count >500/ul was 18 days (range 4–45) and median time to platelet count >20.000/ul was 17 days (range 7–58). Cumulative incidence (CI) of acute GvHD grade II-IV was 45% (95% confidence interval [95CI] 37%–53%) and of chronic GvHD was 41% at 36 months (95CI 33%–49%). Thirty-four patients relapsed: CI: 22% at 5 years (95CI 16%–28%). There was no correlation between telomere length and engraftment, acute or chronic GvHD or relapse. The overall survival was 62% at 5 years (95CI 54%–70%). During the study, 37 patients died due to TRM. TRM rate inversely correlated with telomere length. In the first quartile, the 5-year CI of TRM was 33% (95CI 2%–22%), 20% (95CI, 8%–32%) in the second quartile; 20% (95CI, 8%–32%) in the third quartile; and 12% in the fourth quartile (95CI, 2%–22%) (p=0.06). When quartiles 2, 3 and 4 were pooled, the increased TRM in first quartile was statistically significant (p = 0.017) (Figure 1). In multivariate analysis using competing risk regression, (including age-adjusted telomeres length, disease stage, age, TBI and source of stem cells), age of the recipients (HR: 1.1, 95% CI [.0–1.1, p=0.0001] and age-adjusted telomeres [HR: 0.4, 95% CI [0.2–0.8, p=0.01]) were independently associated with TRM. The same two factors remained significant in subset analysis of patients with malignant diseases (n=154) (p= 0.0004, HR: 1.1 and p=0.018, HR: 0.43, respectively). No association was found between donor telomere length and outcome post HSCT. In conclusion, age-adjusted recipient pre-transplant telomere length is an independent biological marker of TRM after HSCT from related donors using a myeloablative conditioning regimen and cyclosporine-based GvHD prophylaxis. Disclosures: Peffault de Latour: Alexion: Consultancy, Research Funding.

scholarly journals Impact of Modifying Conditioning and Immunosuppressive Strategies in Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5714-5714
Author(s):  
Nawar Dakhallah ◽  
Mylène Beauchemin ◽  
Johanne Richer ◽  
Sonia Cellot ◽  
Pierre Teira ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Gvhd ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Current Approach ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis

Background:Hematopoietic stem cell transplants (HSCT) is indicated for some very high-risk childhood acute lymphoblastic leukemia (ALL) patients in complete remission 1 (CR1) and for patients in >CR2. Relapse remains the most frequent complication after transplant. In 2012, in order to decrease the relapse rate, we modified our conditioning and GVHD prophylaxis regimen. Total body irradiation doses were increased, etoposide removed and fludarabine introduced. Anti-thymocyte globulin (ATG) was removed of GVHD prophylaxis regimen and mycophenolate mofetil was added for unrelated marrow grafts. The aim of this study was to compare outcome between previous (PS) and new strategies (NS) prior and after 2012. Methods: This retrospective study included all 47 patients aged 0 to 18 years old who underwent a first HSCT for ALL at Sainte-Justine University Health Center from 2007 to 2017. Our primary endpoint was 2-year event-free survival (EFS) between PS (n=22) and NS (n=25) groups. Secondary endpoints included overall survival (OS), relapse, GVHD, immunological recovery and infection rates. Results: Demographic parameters and leukemia characteristics were not significantly different between groups. In the PS group, median age was 6.1 years [2.7;13.5] and 41% of patients were female. In the NS group, median age was 7.1 years [2.4;11.4] and 44% of patients were female. B-cell and T-cell lineage leukemias were present in respectively 82% and 18% of PS and 76% and 24% in NS. Fourteen percent of patients were transplanted in CR1 in the PS versus 40 % in the NS group. EFS at 2 and 5 years were respectively 46% and 36% with the PS compared to 60% and 53% with the NS (p=0.170). OS at 5 years was significantly higher with the NS (46% vs 75%, p=0.05). Morphologic relapse rates at 5 years of PS and NS were 55% and 30% (p=0.14). Acute GVHD rate at 6 months was superior with the NS (41% vs 80%, p=0.002). Chronic GVHD rate at 5 years was similar between groups. At least one proven infection at 100 days was documented in 96% compared to 88% of patients with the PS and NS respectively (p=0.08). Neutrophil recovery at 60 days and platelets recovery at 180 days were not significantly different. T-cell Immune recovery at 6 months was superior in the NS. Median (min;max) CD3 counts in PS and NS were respectively 339 (132;1152) versus 946 (284;1944) (p=0.009), CD4 counts were 221 (65;612) versus 594 (238;920) (p=0.046) and CD8 counts were 55 (34;414) versus 320 (210;1104) (p<0.001). Conclusion: Compared to the PS, the NS of conditioning regimen and GVHD prophylaxis shows a significant improvement in OS and a tendency towards decreased relapse and increased EFS. However, we found a significant increase in acute GVHD with this regimen, which is explained by the removal of ATG from the regimen. These results highlight the necessity to adjust our strategy with HSCT ALL with the aim of maintaining graft versus leukemia effect without increasing GVHD. Emerging immunotherapy (such as antibody-based and chimeric antigen receptor T cell therapies) might shift the management of refractory and relapsed ALL and our current approach to HSCT. Disclosures Bittencourt: Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy, Other: Travel, accommodations expenses.

Outcome of Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia in Third Complete Remission (CR3): A Vital Role for Graft-Versus-Host-Disease/Graft-Versus-Leukemia Effect in Survival.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3667-3667
Author(s):  
Adam Gassas ◽  
Kashif Ishaqi ◽  
John Doyle
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Related Mortality

Abstract Children with acute lymphoblastic leukemia (ALL) who suffer 2 relapses could be salvaged by hematopoietic stem cell transplantation (HSCT) when a suitable stem cell source is available provided they respond to the pre HSCT chemotherapy and at least enter morphological remission. However, these patients are at very high risk for post HSCT relapse and also at a high risk for transplant related mortality (TRM). Our objective, herein, was to review the outcome of children (0–18years) with ALL who received allogeneic HSCT in third complete remission (CR3) at our institution. Between January 1994 – August 2005, twenty-two consecutive children in CR3 received HSCT in the Hospital for Sick Children, Toronto, Canada. Conditioning regimens included single dose of VP16 (60mg/kg infused over 4 hours) and fractionated total body irradiation (TBI; 1200cGy) in six fractions over 3 days (VP16/TBI) in 10 patients (1994–1998) and cyclophosphamide 50mg/kg infused over 1 hour daily for 4 days followed by the same dose of fractionated TBI (CY/TBI) in 12 patients (1999–2005). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A and a short course of methotrexate for the majority of patients, and all patients were in complete morphological remission prior to HSCT. Median age was 8.4 years (range 3–15.4). Donor source was as follows: matched sibling donor (MSD), 8; matched unrelated donor (MUD) 6; one antigen mismatch related donor (MMRD) 4; one antigen mismatched unrelated donor (MMUD) 3; and one patient received 1 antigen mismatched cord progenitor stem cells. White cell engraftment was successful in all patients at a median of 18 days (range 9–29). Ten patients died of TRM, seven relapsed, one died from other causes and four patients are long term survivors at a median follow up of 3.7 years (range 1–10.2). All patients who did not develop clinical acute or chronic GVHD relapsed and died. Event free survival was (EFS 19% ± 4%). Three out of the 4 survivors received MMUD and all 4 survivors had moderate to severe acute GVHD and three had chronic GVHD, limited in two and extensive in one. Conclusion: Children with ALL in CR3 receiving HSCT are extremely high risk for relapse and transplant related mortality. These children have already relapsed twice and demonstrated chemotherapy resistance and GVL/GVHD plays a key role in leukemia eradication. Although, TRM is high in such patients and GVHD could potentially increase TRM, there are no survivors without GVHD and exploring means of inducing GVHD by reduction of immunosuppressive medications or other means of immunotherapy should seriously be considered in these patients.

Late Events in Patients with Relapsed or Refractory Hodgkin’s Lymphoma Treated with an Autologous Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 834-834
Author(s):  
Michal Sieniawski ◽  
Andreas Josting ◽  
Carmen Canals ◽  
Anthony H. Goldstone ◽  
Martin Gramatzki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Standard Treatment ◽  
Cox Regression ◽  
Cumulative Risk ◽  
Significant Risk ◽  
Solid Tumours ◽  
Secondary Malignancies ◽  
Cox Regression Analysis ◽  
Related Mortality

Abstract Background: Autologous stem cell transplantation (ASCT) has been used as a standard treatment in the management of patients (pts) with relapsed/refractory Hodgkin’s lymphoma (HL) in the last few decades. Long-term side effects of this treatment such as secondary malignancies (SM), organ failure and infertility attract scientific interest. Very little data is available on late events among pts with HL treated with ASCT. Material and Methods: We retrospectively analysed HL pts treated with an ASCT and registered in the European Group for Blood and Marrow Transplantation (EBMT) Database. Further inclusion criteria were: age at ASCT ≥ 18 years and time of transplantation between 1985 and 1995. Additionally, pts treated with tandem protocols have been excluded. The frequency of late events including incidence of secondary malignancies and non-relapse related mortality (NRM) was evaluated. Univariate and multivariate analyses of risk factors for SM and NRM were performed. Results: 2289 pts (median age at ASCT 30 years, range 18 – 70) were evaluated; 1408 (61.5%) pts were male. Most patients (76.9%) were in complete or partial remission at the time of transplantation and 23.1% of pts were transplanted with refractory or progressive disease. BEAM was the conditioning regimen most frequently used (57.3%) followed by CBV (29.4%) and other chemotherapy regimens (8.7%); TBI was given to 4.7% of pts. Median follow-up for all pts was 47 months (range 0 – 240). Progression free survival and overall survival at 5 years for the whole series were 39.9% and 46.8%, respectively. 988 pts (43.3%) relapsed after a median time of 8.5 months post-ASCT, 787 of them died and 201 are alive after a relapse. 312 pts died without previous relapse or progression (NRM). The main causes of death were relapse/progression (34%), transplant related mortality (11.4%) and SM (1.5%). Cumulative risk at 10 years for NRM was 14.4%. Sex, disease status at ASCT, year of ASCT (1985 – 1990 vs. 1990 – 1995), stem cell source (BM vs. PB), age > 40 years, conditioning with CBV, conditioning including TBI and time of ASCT after diagnosis > 48 months were significant prognostic factors in multivariate Cox regression analysis for NRM. SM were diagnosed in 74 pts (3.2%): solid tumours in 33 pts (1.4%), MDS/acute leukaemias in 35 pts (1.5%) and NHL in 6 pts. Cumulative risk at 10 years for SM was 4.4%, for solid tumours 2.2% and for MDS/acute leukaemia 1.7%. The significant risk factors in multivariate Cox regression analysis for SM were age at ASCT > 40 years, time from diagnosis to ASCT > 48 months and conditioning with CBV (p<0.05). Age > 40 years was the only significant risk factor for solid tumours and MDS/acute leukaemias in Cox multivariate analysis. Conclusions: ASCT remains the standard treatment for patients with refractory/relapsed HL. The cumulative risk at 10 years for NRM and for SM was 14.4% and 4.4%, respectively. The cumulative risk for SM among evaluated patients is higher compared with that reported among HL patients after first line treatment and is expected to increase over time due to the rather short median observation time and the slow progression of solid malignancies.

Cord Blood (CB) Unit Mononuclear Cell (MNC) Dose: Effect on Transplantation Outcome and Relevance to Processing Method and CBU Selection.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1969-1969 ◽  
Author(s):  
Andromachi Scaradavou ◽  
Cladd Stevens ◽  
Ludy Dobrila ◽  
Tracy Zhu ◽  
Shanlong Jiang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cox Regression ◽  
Reference Group ◽  
Cell Number ◽  
Dose Effect ◽  
P Value ◽  
Cox Regression Analysis ◽  
Gvhd Prophylaxis ◽  
Transplant Center ◽  
Related Mortality

Abstract Among the CB graft characteristics that affect post-transplant engraftment and survival TNC dose has become a critical variable in the selection of CB units. However, the cryopreserved TNC depends on the method of CB processing. The AXPTM system, used by the NYBC-NCBP since August 2006, automatically reduces the volume and separates the components of a CB unit in a closed system, resulting in &gt;95% recovery of MNCs, CFU and CD34+ cells and excellent viability, consistently, while the average recovery of TNC is 80%. MNCs represent 47% (±0.07) of the pre-processing TNC. Thus, when processing has no effect on type of cells recovered, a CB unit with a TNC of 900x10^6 (cell number criterion used for inclusion in the National Cord Blood Inventory) would have an average of 425x10^6 MNCs. As a result of the differential recoveries, however, of all CBUs with a pre-processing TNC &gt;1100x10^6, 58% will have a post-processing TNC count ≥ 900x10^6; in contrast, 81.5% will have MNC ≥ 425x10^6 (N=11012 units processed with the AXP system during the period: 2006–2008). To evaluate whether the MNC dose has an impact on transplant outcome, and compare it to that of the TNC dose, we evaluated the effect on time to engraftment (time to ANC ≥ 500) and transplant related mortality (TRM) in all patients with leukemia or myelodysplasia that received single unit CB grafts from our Bank following myeloablative cytoreduction, during the period 1993–2006. A total of 1044 patients (mean age: 13.9 years, median: 9.2 years, range: 0.2–64 years, 22% &gt;20 years) were included, 87% had follow-up data. CBUs had 0 (5%), 1 (33%) or ≥ 2 (61%) HLA mismatches with the recipient; the median cryopreservation TNC/kg was 4.1x10^7. Pre-freezing complete counts were obtained by automated hematology analyzers (H*1, Technicon, Bayer Corporation or Sysmex XE-2100, Roche Diagnostics). Until July 2006, CBUs were processed manually [PNAS 94(22);1995]. For this study, MNC included nucleated RBC. In a multivariate Cox regression analysis TNC/kg, HLA mismatch level, GvHD prophylaxis, transplant center and year were independently predictive of time to ANC ≥ 500. When MNC/kg was added to the analysis with TNC/kg, only the MNC dose was a significant predictor (RR:1.5, p:0.03), and the TNC dose was no longer predictive (p:0.7). Low MNC/kg (&lt;1x10^7) was associated with delayed engraftment; time to ANC ≥ 500 shortened (showed by increasing RR of engraftment) with higher doses of MNC. Similar variables: HLA mismatch level, TNC/kg, race, transplant center and year affected TRM independently, and again, the significant effect of MNC/kg on TRM, when included in the multivariate analysis, removed the significance of TNC dose. As shown, low MNC/kg (&lt;1x10^7) was associated with increased TRM (RR:1.8, p&lt;0.001). Time to ANC ≥ 500 Transplant-related mortality MNC/kg x(10 7 ) N=944 RR (95%CI) p value N=831 RR (95% CI) p value &lt;1.0 154 0.6 (0.5–0.7) &lt;0.001 159 1.8 (1.5–2.2) &lt;0.001 1.0 – 1.9 291 Reference group 309 Reference group 2.0 – 2.9 144 1.0 (0.8–1.1) 0.559 151 0.9 (0.7–1.1) 0.264 3.0 – 3.9 92 1.2 (0.98–1.4) 0.085 99 0.8 (0.6–1.1) 0.192 ≥ 4.0 150 1.7 (1.4–2.0) &lt;0.001 158 0.7 (0.6–0.95) 0.02 MNC dose, therefore, emerges as a better predictor of time to engraftment and TRM than the TNC dose, and thus, as a better measure of graft quality to be used in selecting CBUs for transplantation. In this context, because AXP processing retains more of the MNCs originally present in the CBU than other systems, this processing maybe used as a criterion of CBU quality when both the TNC and MNC are used as indices of CBU cellular contents.

scholarly journals Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2844
Author(s):  
Christopher J. D. Wallis ◽  
Bobby Shayegan ◽  
Scott C. Morgan ◽  
Robert J. Hamilton ◽  
Ilias Cagiannos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
De Novo ◽  
Population Based ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Cognitive impairment predicts conversion to multiple sclerosis in clinically isolated syndromes

2009 ◽  
Vol 16 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Valentina Zipoli ◽  
Benedetta Goretti ◽  
Bahia Hakiki ◽  
Gianfranco Siracusa ◽  
Sandro Sorbi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Prognostic Value ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Clinically Isolated Syndromes ◽  
Kaplan Meier ◽  
Sizable Proportion ◽  
One Year ◽  
Therapeutic Decision Making

Significant cognitive impairment has been found in 20—30% of patients with clinically isolated syndromes suggestive of multiple sclerosis. In this study we aimed to assess the prognostic value of the presence of cognitive impairment for the conversion to multiple sclerosis in patients with clinically isolated syndromes. All patients with clinically isolated syndromes consecutively referred to our centre since 2002 and who had been followed-up for at least one year underwent cognitive assessment through the Rao’s Battery and the Stroop test. Possible predictors of conversion to clinically definite multiple sclerosis were evaluated through the Kaplan Meier curves and Cox regression analysis. A total of 56 patients (41 women; age 33.2 ± 8.5 years; expanded disability scale score 1.2 ± 0.7) were recruited. At baseline, 32 patients (57%) fulfilled McDonald’s criteria for dissemination in space. During the follow-up (3.5 ± 2.3 years), 26 patients (46%) converted to a diagnosis of multiple sclerosis. In particular, 64% of patients failing ≥ 2 tests and 88% of patients failing ≥ 3 tests converted to multiple sclerosis. In the Cox regression model, the failure of at least three tests (HR 3.3; 95% CI 1.4—8.1; p = 0.003) and the presence of McDonald’s dissemination in space at baseline (HR 3.8; 95% CI 1.5—9.7; p = 0.005), were found to be predictors for conversion to multiple sclerosis. We conclude that cognitive impairment is detectable in a sizable proportion of patients with clinically isolated syndromes. In these subjects cognitive impairment has a prognostic value in predicting conversion to multiple sclerosis and may therefore play a role in therapeutic decision making.

scholarly journals Investigating the Relationship between CD34+and CD3+ Cell Doses, One-Year Graft-Versus-Relapse-Free-Survival, Graft-Versus-Host Disease, and Overall Survival in Haploidentical Hematopoietic Stem Cell Transplantation: A Single Center Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2051-2051 ◽  
Author(s):  
Mindy Hsiao ◽  
Anastasia Martynova ◽  
George Yaghmour ◽  
Chris Foss
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Optimal Dose ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Improved Outcomes ◽  
The Mean ◽  
Related Mortality

Background: Haploidentical hematopoietic cell transplantation (haplo-HCT) has emerged as a popular alternative to traditional HLA-matched hematopoietic cell transplant. As the number of haplo-HCT's rises, investigating the factors that may affect outcomes is necessary in order to improve overall survival and reduce transplant-related mortality. The optimal dose of CD34+ cells used during haplo-HCT to ensure favorable outcomes using PTCy has not yet been reported though a range of 2 to 5.00x106 cells/kg is commonly used.Furthermore, the optimal dose of CD3+ cells is unknown however recent data has suggested less than 3.00x108 cells/kg may prevent the development of acute GVHD. The importance of studying the impact of CD34+/CD3+ cell dosing may help to improve outcomes in this setting. Methods: We retrospectively analyzed adult patients at USC Norris Cancer Hospital (age ≥ 21) who received haplo-HCT from 2014 to 2019. The primary end-point assessed was 1-year GVHD-free/relapse-free survival (GRFS) defined as grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the first post-HCT year. Secondary end-points included 1-, 2-, and 3-year relapse-related mortality (RRM) and overall survival (OS) in addition to 1-year transplant related mortality (TRM) and incidence of both acute and chronic GVHD. Results: A total of 67 adult haplo-HCT recipients were reviewed. Of the patients evaluated, approximately 50% (n = 33) were male and 49% (n = 32) were female. The age range was 21-71 years old (median = 44), and the most common underlying hematologic disorders included AML (40%), ALL (38%), aplastic anemia (7.7%), and others (MDS, lymphoma, myelofibrosis, and HLH) (13.8%). 67% of patients received myeloablative conditioning regimens while 33% received reduced intensity regimens. 70% (n = 47) of patients received peripheral blood as a stem cell source with 30% (n = 20) receiving bone marrow. The mean CD34+ dose infused was 6.07x106 cells/kg and the mean CD3+ dose was 2.94x108 cells/kg. The mean time to recovery of platelets, neutrophils, and lymphocytes was 25, 18, and 37 days respectively. CD34+ stem cells ≥5.00x106 cells/kg was significantly associated with shorter time to lymphocyte recovery (p = 0.0265) though recovery less than 30 days was not significantly associated with OS (p = 0.5268). Incidence of 1-year GRFS was 71% (n= 46) and 1-, 2-, and 3-year RRM were 4.6%, 6%, and 7.7% respectively. 1-year TRM was 15.3% with 50% of deaths from acute GVHD. 1-, 2-, and 3-year OS were 80%, 78%, and 77% respectively. Factors significantly associated with increased mortality included use of RIC regimen (p = 0.004) and disease status at time of transplant (p = 0.04). Cumulative incidence of GVHD was 63% (n = 42) with 33% (n = 22) and 30% of patients (n = 20) with acute and chronic GVHD respectively. Lack of mild chronic GVHD was associated with increased mortality (p = 0.0029) and use of a myeloablative regimen (p = 0.0029) was significantly associated with GVHD. Subgroup analysis of those who received CD34+ dose ≥7.00x106 cells/kg (n = 24) and ≥10x106 cells/kg (n = 7) were found to have 1-year OS of 87.5% and 85.7% compared with 77% and 80% in those that received lower doses (p= 0.2229 and p = 1.00) respectively however this was not found to be significantly associated with increased incidence of GVHD, relapse, or mortality. Discussion: Our results demonstrate improved outcomes specifically 71% survived 1 year without experiencing at least 1 GRFS event compared with 24-35% reported by CIBMTR, Holtan et al 2015, and Solh et al 2016 with 3-year OS of 77% when compared with a previously reported 48%. The mean CD34+ cell dose of our population is higher than the standard range which may account for the improved outcomes however the dosing of CD34+/CD3+ cells were not significantly associated with our primary and secondary end-points. It was significantly associated, however, with shorter time to lymphocyte recovery, a factor that has been reported to be associated with decreased RRM and therefore improved OS. Furthermore, subgroup analysis of higher CD34+ dose did show a better 1-year OS though this was not statistically significant. Limitations of this study include small sample size and short follow-up period. Further research with a prospective study identifying the optimal CD34+/CD3+ cell dose in addition to comprehensive evaluation of immune recovery is warranted in order to improve haplo-HCT outcomes. Figure Disclosures Yaghmour: Jazz Pharmaceutical company: Consultancy, Speakers Bureau; Astella company: Speakers Bureau; Takeda: Speakers Bureau.

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