Dianne Pulte

German Cancer Research Center

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Hermann Brenner

German Cancer Research Center

Lina Jansen

German Cancer Research Center

ÁG

Ádám Gondos

Roche (Switzerland)

Kelly J. Norsworthy

United States Food and Drug Administration

Bernd Holleczek

Krebsregister Saarland

Richard Pazdur

United States Food and Drug Administration

Alexander Katalinic

University of Lübeck

Maria Theresa Redaniel

University of Bristol

Ann T. Farrell

Hadassah Medical Center

R. Angelo de Claro

Center for Drug Evaluation and Research

Cooperative Institutions

John Wiley & Sons (United States)

United States Food and Drug Administration

Center for Drug Evaluation and Research

Memorial Sloan Kettering Cancer Center

German Cancer Research Center

Heidelberg University

Cornell University

National Institutes of Health

Harvard University

National Cancer Institute

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Improvement in survival in younger patients with acute lymphoblastic leukemia from the 1980s to the early 21st century

Blood (2008)

Dianne Pulte Ádám Gondos Hermann Brenner

Relative survival

10.1182/blood-2008-06-164863

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Citations (221)

Changes in the survival of older patients with hematologic malignancies in the early 21st century

Cancer (2016)

Dianne Pulte Lina Jansen Felipe A. Castro Hermann Brenner

Survival for patients with hematologic malignancies has improved during the early 21st century. However, it is unclear whether older patients have benefited to the same extent as younger patients. This study examines changes in survival for older patients with the 7 most common hematologic malignancies.Period analysis was used to examine survival for patients who were 65 years old or older and were diagnosed with a common hematologic malignancy between 1992 and 2012 with data from the Surveillance, Epidemiology, and End Results database.Five-year relative survival increased for older patients with hematologic malignancies with the partial exception of acute myelogenous leukemia, for which no change in survival was seen for patients who were 75 years old or older. Patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma, including the oldest patients, had especially strong improvements, with increases in 5-year relative survival for patients who were 85 years old or older of 31.5% and 39.6%, respectively, between 1997-2000 and 2009-2012.Despite these increases, survival rates did not reach those observed for patients aged 50 to 59 years for any hematologic malignancy. Newer therapies and a better understanding of how to treat older patients have led to increased survival expectations for older patients with most hematologic malignancies, but an age-related survival disparity persists. Cancer 2016;122:2031-40. © 2016 American Cancer Society.

Hematologic malignancy

Relative survival

Hematologic Neoplasms

10.1002/cncr.30003

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Citations (54)

Survival of Patients with Chronic Myelocytic Leukemia: Comparisons of Estimates from Clinical Trial Settings and Population-Based Cancer Registries

The Oncologist (2011)

Dianne Pulte Ádám Gondos Maria Theresa Redaniel Hermann Brenner

Abstract Introduction. The survival of patients with chronic myelocytic leukemia (CML) has improved during the past decades. However, there have been discrepancies between results reported from clinical trials and population-based studies. We aimed to elucidate the extent of these discrepancies. Methods. We examined the 5-year survival rate of patients in clinical trials of CML treatment and compared these results with the survival of patients in the general population using the Surveillance, Epidemiology, and End Results (SEER) database, correcting for differences in the age structure of the patient populations. Results. Twenty-nine trials were identified for data extraction. The survival rate calculated from SEER data was lower than the survival rate in clinical trials in the corresponding period, with differences of 2.1%–50.7%. Age-adapted survival was similar for four trials, but differences up to 35.8% were seen in most. Limitations of the study include the lack of information on chemotherapy in the SEER database and possible heterogeneity of cases. Discussion. The survival rate in clinical trials of CML treatment is higher than the survival rate of all patients with CML. We speculate that the difference may be a result of access to better medications, selection of healthier patients for trials, and the time necessary for adoption of new treatments. This finding underscores the need for population-based studies to give a more realistic idea of survival for patients with a given malignancy in the general population.

Relative survival

10.1634/theoncologist.2010-0393

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Citations (33)

Ikaros increases normal apoptosis in adult erythroid cells

American Journal of Hematology (2005)

Dianne Pulte Rocío López Shane T. Baker Maureen Ward Ellen K. Ritchie

Abstract Ikaros is a critical transcriptional regulator of hematopoietic cell differentiation. In addition to its effects on the lymphoid system and hematopoietic stem‐cell compartment, we have previously shown that Ikaros is also required for normal erythroid development. In this report, we compare Ikaros‐dependent gene expression in erythroid cells of mice lacking the Ikaros protein with that of normal mice in purified adult bone‐marrow erythroid cells (BMRC). Gene expression, measured by Affymetrix microarray analysis, indicates that in the BMRC of Ikaros‐null mice, there is significant up‐regulation of SMADs 6 and 7, serine protease inhibitor 3, and immediate–early protein 3 (IER3), all proteins that play a modulating role in apoptosis. We investigate the role of Ikaros in oxidative stress‐induced apoptosis using Annexin‐V staining and FACS analysis. We find a decrease in apoptosis in the BMRC of Ikaros‐null mice compared to normal mice. This effect is also seen in nonerythroid cells but is stronger in BMRC. We conclude that normal Ikaros function increases normal apoptosis in erythroid cells. The data also suggest that Ikaros plays a role in apoptosis‐mediated events in other normal hematopoietic cell lineages. Am. J. Hematol. 81:12–18, 2006. © 2005 Wiley‐Liss, Inc.

Null cell

10.1002/ajh.20507

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Citations (11)

Survival of Adults with Acute Lymphoblastic Leukemia in Germany and the United States

PLoS ONE (2014)

Dianne Pulte Lina Jansen Ádám Gondos Alexander Katalinic Benjamin Barnes

Adulthood acute lymphoblastic leukemia (ALL) is a rare disease. In contrast to childhood ALL, survival for adults with ALL is poor. Recently, new protocols, including use of pediatric protocols in young adults, have improved survival in clinical trials. Here, we examine population level survival in Germany and the United States (US) to gain insight into the extent to which changes in clinical trials have translated into better survival on the population level.Data were extracted from the Surveillance, Epidemiology, and End Results database in the US and 11 cancer registries in Germany. Patients age 15-69 diagnosed with ALL were included. Period analysis was used to estimate 5-year relative survival (RS).Overall 5-year RS was estimated at 43.4% for Germany and 35.5% for the US (p = 0.004), with a decrease in survival with increasing age. Survival was higher in Germany than the US for men (43.6% versus 37.7%, p = 0.002) but not for women (42.4% versus 40.3%, p>0.1). Five-year RS estimates increased in Germany and the US between 2002 and 2006 by 11.8 and 7.3 percent units, respectively (p = 0.02 and 0.04, respectively).Survival for adults with ALL continues to be low compared with that for children, but a substantial increase in 5-year survival estimates was seen from 2002 to 2006 in both Germany and the US. The reasons for the survival differences between both countries require clarification.

Relative survival

10.1371/journal.pone.0085554

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Citations (103)

Changes in long term survival after diagnosis with common hematologic malignancies in the early 21st century

Blood Cancer Journal (2020)

Dianne Pulte Lina Jansen Hermann Brenner

Abstract Five-year survival has increased for many hematologic malignancies in the 21st century. However, whether this has translated into greater long-term survival is unknown. Here, we examine 10- and 20-year survival for patients with multiple myeloma (MM), acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoid leukemia (CLL), chronic myeloid leukemia (CML), non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL). Data were extracted from the Surveillance, Epidemiology, and End Results-9 database. Patients age 15+ with the above malignancies were included. The newly developed boomerang method was used to examine 10- and 20-year relative survival (RS) for patients in 2002–2006 and 2012–16. Ten and 20-year RS increased for each malignancy examined, with increases ranging from +4.4% units for 20-year RS for AML to +23.1% units for 10-year RS for CML. Ten year RS was >50% in 2012–16 for patients with CLL, CML, HL, NHL, and DLBCL, at 77.1%, 62.1%, 63.9%, 64.5%, and 63.0%, respectively. Survival dropped between 10 and 20 years after diagnosis for most malignancies. Long-term survival is increasing for common hematologic malignancies, but late mortality is an ongoing issue. Further study of long-term outcomes in curable malignancies to determine the reason for these later decreases in survival is indicated.

Hematologic malignancy

Acute myeloblastic leukemia

Relative survival

Hematology

10.1038/s41408-020-0323-4

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Citations (120)

Role of Intergenic Human γ‐δ‐Globin Sequences in Human Hemoglobin Switching and Reactivation of Fetal Hemoglobin in Adult Erythroid Cells

Annals of the New York Academy of Sciences (2005)

Arthur Bank David O’Neill Rocío López Dianne Pulte Maureen Ward

A bstract : The details of the molecular events regulating normal human hemoglobin switching and reactivation of fetal hemoglobin in adult hematopoietic cells are unclear. The potential role of sequences between the human γ‐ and δ‐globin genes (intergenic γ‐δ sequences) in this process has been in question until the recent finding that two patients homozygous for the Corfu deletion, involving the loss of 7.2 kb of the intergenic γ‐δ region upstream of the δ gene, have 88% and 90% fetal hemoglobin, only mild anemia, and no transfusion requirements. These results provide the first strong evidence in humans that the γ‐δ intergenic sequences alone have a role in the reactivation of fetal hemoglobin in adult‐type cells, and perhaps are involved in normal hemoglobin switching as well. The polypyrimidine (PYR) complex is a hematopoietic cell‐specific and stage‐specific chromatin remodeling complex that binds upstream of the human δ‐globin gene within the Corfu deletion. Deletion of the PYR binding site has been shown to delay human γ‐to‐β globin switching. The PYR complex is present in adult human hematopoietic cells and absent in fetal‐embryonic cells: properties of a globin‐switching complex. Taken together, the data from patients with the Corfu deletion and the PYR complex results suggest that intergenic γ‐δ sequences are involved in human γ‐to‐β globin switching and reactivation of fetal hemoglobin in adult cells.

Intergenic region

10.1196/annals.1345.057

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Citations (21)

Improvement In Survival of Patients with Multiple Myeloma: An Update of Population Based Survival Trends

Blood (2010)

Dianne Pulte Ádám Gondos Hermann Brenner

Relative survival

10.1182/blood.v116.21.1510.1510

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Citations (0)

Improved population level survival in younger Hodgkin lymphoma patients in Germany in the early 21st century

British Journal of Haematology (2014)

Dianne Pulte Lina Jansen Ádám Gondos Katharina Emrich Bernd Holleczek

Summary Treatment for Hodgkin lymphoma ( HL ) is more aggressive in Germany than in the United States ( US ) and differences in treatment may lead to differences in population level survival. Patients diagnosed with HL in 11 German states in 1997–2006 were included in the analyses and were compared to similar analyses from patients in the Surveillance, Epidemiology, and End Results database in the US . Period analysis was used to calculate 5‐year relative survival for the time period of 2002–2006 overall and by gender, age and histology. Overall 5‐year relative survival for patients with HL in Germany was 84·3%, compared to 80·6% for the US . Survival was highest in patients aged 15–29 years at 97·9% and decreased with age to 57·5% at age 60 + Survival for men and women, respectively, was 84·7% and 84·1% in Germany and 78·2% and 83·6% in the US . 5‐year relative survival for patients diagnosed with HL in Germany was close to 100% for younger patients. Survival of HL patients in the US was lower than in Germany overall, but was comparable in older patients and in women. Population‐based studies with longer follow‐up are still needed to examine effects of late toxicity on long term survival.

Relative survival

10.1111/bjh.12722

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Citations (22)

Survival of patients with lymphoplasmacytic lymphoma and solitary plasmacytoma in Germany and the United States of America in the early 21 ^st century

Haematologica (2017)

Janick Weberpals Dianne Pulte Lina Jansen Sabine Luttmann Bernd Holleczek

Population-level survival has increased for a number of hematologic malignancies.[1][1]–[3][2] Multiple myeloma, in particular, has seen improved survival both in clinical trials[4][3]–[8][4] and on the population level.[3][2],[9][5]–[11][6] However, it is not known whether the changes in

Lymphoplasmacytic Lymphoma

10.3324/haematol.2016.157768

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Citations (8)