Prognosis in Acute Myeloid Leukemia: A Population-Based Study on 5,809 Patients Diagnosed in Sweden 1973–2001.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1845-1845 ◽  
Author(s):  
Asa R. Derolf ◽  
Ola Landgren ◽  
Paul Dickman ◽  
Sigurdur Y. Kristinsson ◽  
Magnus Bjorkholm

Abstract Background AML is an aggressive disease, which is rapidly fatal without specific therapy. Such treatment was not available until the early 1970’s when combinations of anthracyclines and cytarabine were introduced. Since then major improvements have been made in chemotherapy, stem cell transplantation (SCT) and supportive care. The aim of this study was to define the impact of modern AML treatment strategies on outcome. Extrapolation of results from clinical trials may not be appropriate for estimation of outcome in the whole population because of a varying degree of patient selection. In this study relative survival rates (RSR) were estimated in relation to age, sex, calendar period and region of residence in a cohort of 5,809 AML patients. Methods Records on all patients with AML reported to the Swedish Cancer Register between 1973 and 2001 were linked to the nationwide Cause of Death Register. Information on the number of SCT in AML patients in Sweden during the study period was obtained from the EBMT register. Survival analysis were performed by computing relative survival rates (RSR), defined as the ratio of observed survival of the patients in the cohort versus the expected survival among individuals of the same age, sex, and calendar year of observation. Results 5809 AML patients diagnosed between January 1, 1973 and December 31, 2001 were identified. The cases were divided into six age groups; 0–18, 19–40, 41–60, 61–70, 71–80, and 80+ years. The study period was arbitrarily divided into 7-year intervals. Improvement was seen in all age groups but the eldest. However, patients < 60 years benefited most from new treatment strategies (table 1). There was a marked increase in SCT during the study period with allogeneic SCT dominating in the last period (fig 1). A comparison between regions (with different therapeutical traditions) was made. The regions of Stockholm, Uppsala and Örebro have cooperated since 1971 within the Leukemia Group of Middle Sweden (LGMS) and was therefore considered as one region and compared with the rest of the country. During the first calendar period the 5-year RSR of residents with AML in LGMS counties was significantly higher than that of patients in remaining regions. However, this difference has disappeared with time. Conclusion Improvement in overall survival of AML patients was mainly confined to young patients (<60 years). However, among patients 60–71 years at diagnosis, a slightly improved RSR was observed. For patients above the age of 70 years, the prognosis remains very poor stressing the fact that the decision to use aggressive chemotherapy for this group of patients should consider the risk of iatrogenic morbidity and mortality as well as projected benefit. The early creation of a cooperative clinical AML group probably explains the improved RSR rates during the first study period (1973–1979). Table 1. Five-year RSR (%) according to age group and calendar period calendar period/age group (years) 1973–1979 1980–1986 1987–1993 1994–2000 0–18 17 31 52 68 19–40 14 17 38 58 41–60 7 13 22 36 61–70 6 8 12 15 71–80 3 3 7 6 81+ 1 0 0 1 Fig. 1 Number of stem cell transplantation in Sweden 1973–2001 Fig. 1. Number of stem cell transplantation in Sweden 1973–2001

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3968-3968 ◽  
Author(s):  
Justin LaPorte ◽  
Stacey Brown ◽  
Xu Zhang ◽  
Asad Bashey ◽  
Lawrence E. Morris ◽  
...  

Abstract Multiple myeloma is the second most common hematological malignancy in the United States. The risk of developing multiple myeloma increases with age; with approximately 85% of patients are over age 55 and 62% over age 65. Through improved supportive care, increased access to hematopoietic stem cell transplantation, and introduction of new biologic agents, survival has increased over the past 20 years. Currently, autologous stem cell transplantation (ASCT) is the standard of care after primary therapy for eligible patients. Research has suggested a greater survival benefit after ASCT for patients < 60 years, but the role of ASCT in older individuals remains less clear. In order to better understand the impact of age on the outcome of myeloma patients receiving ASCT, we analyzed the presenting features and outcomes of 256 consecutive patients at our institution that received a first ASCT between January 2004 and December 2013. Patient characteristics were: median age 61 (range 32-76), Sex: M=55% F=45%, Immunochemical subtype: IgG=59%, IgA =21%, Light chain=16%, Other=4%, Durie-Salmon System (DSS) stage at diagnosis: Stage I=9%, Stage II=20%, Stage III=68%, Unknown=4%, Disease status at transplant: CR/sCRsp=18%, VgPR=27%, PR=49%, Stable=6%, Melphalan preparative dose: 200mg/m2=93%, 140mg/m2=7%. Second ASCT was eventually performed in 60 (23%) of patients, with 39 (15%) of these being planned tandem ASCT. Patient survival and disease status were collected prospectively as part of our comprehensive database. For purposes of analysis, patients were divided by age into three groups: age<55 (n=80), age 55-64 (n=90), age ≥ 65 (n=86). Groups were similar in regards to disease subtype, stage, status at the time of transplant, comorbidity index, and year of transplant; differences included more second transplants and tandem transplants in the youngest age group and more reduced dose melphalan in the oldest age group. At day +100 post-transplant, disease response was CR, VGPR, PR, and <PR in 35%, 24%, 39%, and 2%, respectively and did not differ statistically by age group. Non-relapse mortality at one-year post-transplant was 1%, and did not differ among the <55, 55-64, and ≥ 65 age-groups (0%, 3%, and 0%, respectively). With a median follow-up of 39 months, the estimated 4-year OS, DFS, and relapse incidence (RI) was 73%, 43%, and 48%, respectively. Survival and RI were significantly better in the younger age group (4-yr OS 84%, 70%, 64%; DFS 58%, 35%, 39%; RI 34%, 53%, 53%, respectively in the <55, 55-64, and ≥ 65 age-groups; see figure). Outcomes were extremely favorable in patients <55 years of age transplanted in CR or VGPR with a 4-yr OS, DFS, and RI of 96%, 75%, and 21%, respectively. Even in the older age groups, median overall survival had not been reached by 5 years, suggesting that all age groups benefit from ASCT. There were no statistically significant differences in measured outcomes between patients age 55-64 years and those age ≥ 65 years, confirming that age ≥ 65 years should not be used to determine transplant eligibility. In multivariate analysis, variables predictive of OS included age, disease stage, and year of transplant; whereas for DFS, predictive variables also included disease status at transplant and planned tandem ASCT (see table). This analysis builds on a growing body of evidence suggesting improved outcomes in patients with multiple myeloma. Patients regardless of age appear to benefit from ASCT, with median survival now exceeding 5 years in all age groups. Patients less than 55 years of age and particularly those achieving at least a VGPR prior to ASCT seem to represent a patient population with an extremely favorable prognosis post-transplant. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.


Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 507-519 ◽  
Author(s):  
Anas Younes

AbstractAlthough classical Hodgkin lymphoma (HL) is considered one of the most curable human cancers, the treatment of patients with relapsed and refractory disease, especially those who relapse after autologous stem cell transplantation, remains challenging. Furthermore, because the median age of the patients is in the mid-30s, the impact of early mortality on the number of years lost from productive life is remarkable. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities. New drugs and novel treatment strategies that are based on our understanding of the disease biology and signaling pathways are needed to improve treatment outcome for these patients. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19020-e19020
Author(s):  
Josephine Emole ◽  
Leyla Shune ◽  
Oleksandra Lupak ◽  
Ajoy Lawrence Dias

e19020 Background: Allogeneic stem cell transplantation (alloSCT) is increasingly being offered to older patients with acute myeloid leukemia (AML) due to availability of reduced-intensity conditioning regimens and better supportive care. Though studies have shown improving alloSCT survival outcomes in older age groups, it is still not known if older age confers higher mortality and morbidity during transplant hospitalization. We queried a national inpatient database to evaluate in-hospital mortality and resource utilization during alloSCT for AML in patients >70 years compared to a younger age group. Methods: We conducted a retrospective study of alloSCT for AML patients ≥ 18 years using the 2018 National Inpatient Sample database. Hospitalizations were selected using International Classification of Disease, tenth revision (ICD-10) codes. Demographics, comorbidities, transplant, and outcome variables were compared between a reference age group (18-70 years) and a comparator group (> 70 years). Study outcomes were in-hospital mortality, length of stay (LOS) and transplant complications. Regression models were fit to assess the association between predictors and outcomes. Results: During the study period, 2610 alloSCT met the inclusion criteria. This cohort consisted of 50% males and 77% Caucasians. Only 7% of these alloSCT were performed for patients > 70 years. Patients >70 yrs had a lower proportion of females compared to the reference age group (32% versus 52%, p<0.01). There were no significant differences in racial distribution, Charlson comorbidity index or median income between the 2 age groups. In-hospital mortality rates for the reference age group versus >70 years were 3% and 5% respectively (p=0.35). In a multivariable model, we found no association between age >70 years and in-hospital transplant mortality. Acute graft versus host disease was more frequent among the reference age group (14% versus 2%, p=0.04), but there were no differences in LOS or rates of graft failure, respiratory failure, sepsis, and acute renal failure between the 2 groups. Conclusions: Despite similar in-hospital transplant outcomes as their younger counterparts, patients >70 years comprised only a small proportion of alloSCT performed for AML in our study. Females were more disproportionately affected by this age disparity. More studies are necessary to identify barriers to alloSCT for older AML patients, more so for older females.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2030-2030
Author(s):  
Mario Delia ◽  
Domenico Pastore ◽  
Anna Mestice ◽  
Paola Carluccio ◽  
Tommasina Perrone ◽  
...  

Abstract Abstract 2030 Background: The therapeutic efficacy of allogeneic stem cell transplantation (alloSCT) for hematological malignancies relies largely on the graft versus leukemia (GvL) effect exerted by the donor CD3 cells, but an uncontrolled graft-versus-host-disease (GvHD) bears a risk of complications. On the other hand, T regs cells (CD4+CD25high Foxp3+) are believed to maintain tolerance and to inhibit GvHD after alloSCT; also, the Foxp3 gene encodes a transcription factor that is a key for thymic development, so T regs cells could preserve an optimal microenviroment for the reconstitution of functional immunity after alloSCT. Moreover, when looking at post allotransplant patients' outcomes, while it is largely known the impact of acute GVHD (triggered by CD3 donor T cells) on survival, there is no evidence that donor graft CD3/T regs ratio may determine an effect in terms of OS, NRM and relapse free survival rates so far. Patients and Methods: In this study we analyzed the graft CD3+/Tregs ratio (gCD3/Tregs R) and determined its impact on acute GVHD (aGVHD), immunological recovery and survival rates (OS, NRM and Relapse) after myeloablative alloPBSCT. We analyzed 74 consecutive patients transplanted with unmanipulated peripheral blood stem cells from an HLA identical related donor (n=48) or an HLA identical unrelated donor (n=26); diagnoses were acute myeloid leukaemia (n=62), acute lymphoblastic leukaemia (n=13). The median CD3+ and Tregs dose administered was 238 (range (r): 67–550) and 12,5×106̂/Kg (r: 2–21), respectively; the median gCD3/Tregs R was 19 (r: 8–250). Patients were subdivided into a high gCD3/Tregs R (>=36) group (HR group n= 30) and a low gCD3/Tregs R (<36) (LR group n=44). Results: The incidence of aGVHD (grade II-IV) in the low gCD3/Tregs R (LR) group was lower than in the high gCD3/Tregs R (HR) group (4/30 or 13% vs 36/44 or 82%, p<.001). The OS, NRM and relapse rate at 3 years was 54,29 and 34%, respectively. Comparing LR with HR group a statistically significant difference is demonstrated for OS and NRM rates (65 vs 31%,p<.004; 3 vs 71%, p<.001), respectively, but not for the R one (35 vs 30%, p=ns). Comparing aGVHD+ with aGVHD- group OS, NRM and relapse were always statistically significant different (39 vs 65%,p<.005; 61 vs 7%,p<.001; 9 vs 53%,p<.002). Conclusions: Taken together, our data may suggest that Tregs content is able to mediate protective effects against aGVHD, while preserving GvL effects as demonstrated by relapse rate comparison between H and LR groups. However, larger studies are needed to understand the real contribution of gCD3/Tregs R on survival rates. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 10 (5) ◽  
pp. 1113
Author(s):  
Kinga Musiał ◽  
Krzysztof Kałwak ◽  
Danuta Zwolińska

Background: Knowledge about the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on renal function in children is still limited. Objectives: The aim of the study was to evaluate kidney function in children undergoing alloHSCT, with special focus on differences between patients transplanted due to oncological and non-oncological indications. Materials and Methods: The data of 135 children undergoing alloHSCT were analyzed retrospectively. The serum creatinine and estimated glomerular filtration rate (eGFR) values were estimated before transplantation at 24 h; 1, 2, 3, 4 and 8 weeks; and 3 and 6 months after alloHSCT. Then, acute kidney injury (AKI) incidence was assessed. Results: Oncological children presented with higher eGFR values and more frequent hyperfiltration rates than non-oncological children before alloHSCT and until the 4th week after transplantation. The eGFR levels rose significantly after alloHSCT, returned to pre-transplant records after 2–3 weeks, and decreased gradually until the 6th month. AKI incidence was comparable in oncological and non-oncological patients. Conclusions: Children undergoing alloHSCT due to oncological and non-oncological reasons demonstrate the same risk of AKI, but oncological patients may be more prone to sustained renal injury. Serum creatinine and eGFR seem to be insufficient tools to assess kidney function in the early post-alloHSCT period, when hyperfiltration prevails, yet they reveal significant differences in long-term observation.


Author(s):  
Hao Dai ◽  
Olaf Penack ◽  
Aleksandar Radujkovic ◽  
David Schult ◽  
Joshua Majer-Lauterbach ◽  
...  

AbstractHyperbilirubinemia occurs frequently after allogeneic stem cell transplantation. Causes include primary liver damage and endothelial complications as major contributors. Here, we have investigated the impact of early bilirubinemia (EB) on posttransplant outcomes. Maximum total bilirubin levels (days 0–28) were categorized using maximally selected log rank statistics to identify a cut off for the endpoint non-relapse mortality (NRM) in a training cohort of 873 patients. EB above this cut off was correlated with NRM and overall survival (OS) and with pre- and posttransplant Angiopoietin-2, interleukin (IL)18, CXCL8 and suppressor of tumorigenicity-2 (ST2) serum levels, and the endothelial activation and stress index (EASIX). Clinical correlations were validated in a sample of 388 patients transplanted in an independent institution. The EB cut off was determined at 3.6 mg/dL (61.6 µM). EB predicted OS (HR 1.60, 95% CI 1.21–2.12, p < 0.001), and NRM (CSHR 2.14; 1.28–3.56, p = 0.004), also independent of typical endothelial complications such as veno-occlusive disease, refractory acute graft-versus-host disease, or transplant-associated microangiopathy. However, EB correlated with high Angiopoietin-2, EASIX-pre and EASIX-day 0, as well as increased levels of posttransplant CXCL8, IL18, and ST2. In summary, EB indicates a poor prognosis. The association of EB with endothelial biomarkers suggests an endothelial pathomechanism also for this posttransplant complication.


Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2003-2008 ◽  
Author(s):  
Michael Boeckh ◽  
W. Garrett Nichols

AbstractIn the current era of effective prophylactic and preemptive therapy, cytomegalovirus (CMV) is now a rare cause of early mortality after hematopoietic stem cell transplantation (HSCT). However, the ultimate goal of completely eliminating the impact of CMV on survival remains elusive. Although the direct effects of CMV (ie, CMV pneumonia) have been largely eliminated, several recent cohort studies show that CMV-seropositive transplant recipients and seronegative recipients of a positive graft appear to have a persistent mortality disadvantage when compared with seronegative recipients with a seronegative donor. Recipients of T-cell–depleted allografts and/or transplants from unrelated or HLA-mismatched donors seem to be predominantly affected. Reasons likely include both incomplete prevention of direct and indirect or immunomodulatory effects of CMV as well as consequences of drug toxicities. The effect of donor CMV serostatus on outcome remains controversial. Large multicenter cohort studies are needed to better define the subgroups of seropositive patients that may benefit from intensified prevention strategies and to define the impact of CMV donor serostatus in the era of high-resolution HLA matching. Prevention strategies may require targeting both the direct and indirect effects of CMV infection by immunologic or antiviral drug strategies.


Blood ◽  
2021 ◽  
Author(s):  
Mariapia A Degli-Esposti ◽  
Geoffrey R Hill

The reactivation of viruses from latency after allogeneic stem cell transplantation (SCT) continues to represent a major clinical challenge requiring sophisticated monitoring strategies in the context of prophylactic and/or pre-emptive antiviral drugs that are associated with significant expense, toxicity, and rates of failure. Accumulating evidence has demonstrated the association of polyfunctional virus-specific T-cells with protection from viral reactivation, affirmed by the ability of adoptively transferred virus-specific T-cells to prevent and treat reactivation and disease. The roles of innate cells (NK cells) in early viral surveillance, and dendritic cells in priming of T-cells have also been delineated. Most recently, a role for strain-specific humoral responses in preventing early cytomegalovirus (CMV) reactivation has been demonstrated in preclinical models. Despite these advances, many unknowns remain: what are the critical innate and adaptive responses over time, is the origin (e.g. recipient versus donor) and localization (e.g. in parenchymal tissue versus lymphoid organs) of these responses important, how does GVHD and the prevention/treatment thereof (e.g. high dose steroids) impact the functionality and relevance of a particular immune axis, do the immune parameters that control latency, reactivation and dissemination differ, and what is the impact of new antiviral drugs on the development of enduring antiviral immunity. Thus, whilst antiviral drugs have provided major improvements over the last two decades, understanding the immunological paradigms underpinning protective antiviral immunity after SCT offers the potential to generate non-toxic immune-based therapeutic approaches for lasting protection from viral reactivation.


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