Sequelae and post-thrombotic syndrome after venous thromboembolism in acute lymphoblastic leukemia survivors treated on the NOPHO ALL2008 protocol.

The treatment of acute lymphoblastic leukemia (ALL) is frequently complicated by toxicity, including venous thromboembolism (VTE) affecting roughly 8% of patients. VTE can lead to post-thrombotic syndrome (PTS), a group of signs and symptoms developed as a complication to deep venous thrombosis (DVT), imposing risk of permanent disability and reduced quality of life (QoL). PTS prevalence ranges from 0% to 70%, reflecting very heterogenous cohorts and assessment tools. We aimed to estimate sequelae, including PTS and QoL in children and adults (<45 years old) who had a DVT during ALL treatment. PTS and QoL scores were obtained through use of Villalta and Modified Villalta Scale, PedsQL, and Short Form-36 questionnaires. The cohort comprised 20 children (<18 years) and seven adults (median age: 12.9 years, range: 2-44 years) at the time of DVT diagnosis. In total, 25 ALL survivors underwent PTS examination. The examination took place when survivors were 7-48 years (median age: 20.3 years, median follow-up time 6.8 years). QoL was assessed correlating cases with three matching ALL survivors without VTE. Two adults (15.4%) showed mild or moderate PTS. Eight children (66.7%) were diagnosed with mild PTS, while three cases had collaterals as sole symptoms. Pain or symptoms affecting daily life were reported by 16%. No difference in QoL was found (p = .9). This study underscores the need for comprehensive population-based investigations with validation of PTS instruments in ALL survivors.

Impact of body mass index on outcome and treatment-related toxicity in young adults with acute lymphoblastic leukemia.

BACKGROUND: Data on outcome for patients in different body mass index (BMI) categories in young adults with acute lymphoblastic leukemia (ALL) are scarce. We explored survival and toxicities in different BMI categories in young adults with ALL. MATERIAL AND METHODS: Patients aged 18-45 years, diagnosed with ALL between July 2008 and June 2022 in the Nordic countries, Estonia, or Lithuania, and treated according to the NOPHO ALL2008 protocol, were retrospectively enrolled and classified into different BMI categories. Endpoints were overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse as well as incidence rate ratio (IRR) of severe predefined toxic events, and treatment delays. RESULTS: The group comprised 416 patients, of whom 234 (56%) were stratified to non-high-risk (non-HR) treatment. In the non-HR group, patients with severe obesity, BMI ≥35 kg/m2 had worse EFS due to relapses but there was no effect on toxicity or treatment delays compared with the healthy-weight patients. There was no association between BMI category and OS, overall toxicity, or treatment delays in the patients with high-risk treatment. CONCLUSION: Severe obesity is associated with worse EFS in young adults treated according to the non-HR arms of the NOPHO ALL2008 protocol. Poorer outcome is explained with a higher risk of relapse, possibly due to under treatment, and not caused by excess therapy-related mortality.

Acute de novo Leukemia in Estonia and Western Sweden 1982-2006: Positive Trend in the Survival of Acute Leukemia over 25 Years.

This study focuses on the incidence, treatment, and survival of de novo acute leukemia in a 25-year perspective in western Sweden and Estonia. At the beginning of our study, Estonia was a part of the Eastern bloc with planned economy, but since 1991 it is a member of the European Union and transforming into a market economy. Survival rates have steadily increased in both countries. However, a gap between their survival curves remains. Based on our data, it is difficult to explain the big difference in the 5-year relative survival in favor of western Sweden (55 vs. 22%). In Germany, there was a big difference in overall cancer survival between East and West Germany after the fall of the iron curtain, but today no difference is seen. Differences in survival are probably due to a higher proportion of intense chemotherapy regimens and a higher rate of hematopoietic stem cell transplantations in Sweden. Other important factors might be better supportive care and diagnostics as well as better adjuvant therapy. Better staff training and conditions in wards are also factors that might play an essential role.

Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia.

OBJECTIVES: Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults. METHODS: We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs treated according to the Nordic/Baltic ALL2008 protocol. RESULTS: No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high-risk blocks (median number of days for patients 1-9, 10-17, and 18-45 yrs; the glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs compared with children 1-9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10-14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001). CONCLUSION: Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents.

Sequential population-based studies over 25 years on the incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1982-2006: a survey of patients aged ≥65 years.

Estonia regained independence in 1991 after five decades of occupation by the Soviet Union. The present population-based survey was carried out over five consecutive 5-year study periods (1982-2006) on the incidence and survival of de novo acute leukemia patients aged ≥65 years at diagnosis in Estonia and in a well-defined area in western Sweden. During the study period of retrospective work (1982-1996), the first 10 years were carried out while Estonia was still under the mentorship of the Soviet Union. Over these years, Estonian hematologists did not have access to therapeutic measures readily available to Swedish hematologists, and the results for survival for western Swedish patients with acute myeloid leukemia (AML) far exceeded those of their Estonian counterparts. However, the results for acute lymphoblastic leukemia were equally dismal in the two countries. Subsequent prospective population-based studies were carried out during the years 1997-2006. A gradual improvement as to long-term relative survival of the Estonian AML patients was observed. When studying 2002-2006, no difference as regards relative survival at 5 years was anymore present between the two countries. Over the first 20 years of our population-based studies, it was repeatedly observed that the age-standardized incidence rate particularly for de novo AML was considerably higher for the western Swedish as compared to the Estonian cohorts. During the last 5-year study period (2002-2006), no such difference between the two countries was present, indicating that some true changes in the reporting procedure in Estonia had occurred.

The incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1997-2001: a survey of patients aged 16-64 years.

BACKGROUND: In a recent retrospective study, we investigated the incidence and survival of de novo acute leukemia (AL) patients aged 16-64 years over three 5-year periods (1982-1996) in Estonia and in the Western Swedish Health Care Region. The incidence rates were similar in the two countries, but the survival data were highly different. Thus, relative survival at 5 years for de novo AL patients in Estonia was virtually negligible, whereas the corresponding figures for the Swedish patients increased from 20.3 to 38.9% during the study period. AIM: To prospectively compare the results for incidence and outcome of de novo AL between the two countries during 1997-2001. RESULTS: Incidence rates for de novo AL were lower in Estonia than in western Sweden but not significantly so. However, the survival for de novo AL patients in Estonia had improved considerably, with the relative survival at 5 years being 16.4%; such improvement was particularly seen in acute myeloid leukemia patients. For the Swedish patients, no change in survival was recorded. CONCLUSION: In Estonia, a remarkable improvement in outcome for young de novo AL patients was seen after 1996. Nevertheless, relative survival for the Estonian patients had still not reached the levels found in the Swedish cohort.

The incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1997-2001: a survey of patients aged >or=65 years.

BACKGROUND: In a recently published retrospective population-based study over three 5-year periods (1982-1996) we investigated the outcome for de novo acute leukemia (AL) patients aged >or=65 years at diagnosis in Estonia (a country that had been occupied by the Soviet Union over 5 decades) and in the so-called Western Swedish Health Care Region. The age-standardized yearly incidence rates regarding the total number of de novo AL was 5.3/100000 inhabitant for Estonia and 8.0 for Sweden, this difference being statistically significant merely as regards acute myeloid leukemia (AML). The relative survival for the total cohort of de novo AL as well as for de novo AML was significantly longer (p<0.001) for Swedish as compared to Estonian patients. METHODS: In view of the miserable outcome for the Estonian patients we decided to prospectively compare the results for incidence and outcome of de novo AL between the two countries. RESULTS: The present report covers the first 5-year period comprising 1997-2001 and deals only with patients aged >or=65 years at diagnosis. The age-adjusted annual incidence rates for de novo AML were lower in Estonia (6.4/100000) than in Sweden (9.2/100000) but not significantly so. The present results also show that the outcome for the Estonian AML patients had improved considerably over the study period; thus, at no time point, i.e., at 1, 3 and 5 years did relative survival between the two countries differ significantly. CONCLUSION: Yet, as compared to the Swedish cohort relative survival for the Estonian patients did still not reach an acceptable level.

The incidence and survival of acute de novo leukaemias in Estonia and in a well defined region of Western Sweden during 1982-1996: a survey of patients aged 16-64 years.

In the present work the incidence and survival of acute de novo leukaemias in two neighbouring countries, were studied retrospectively over three 5-year periods, 1982-1996. The aim was to compare the above variables, particularly with respect to political/socio-economic and environmental factors, in a well defined area of Sweden, the so-called Western Swedish Health Care Region, with Estonia. Population-wise the Western Swedish Region and Estonia are very similar; area-wise they are also well comparable. The present report covers only patients diagnosed between the ages of 16-64 years. The number of acute de novo leukaemias in the two regions was quite similar (Western Sweden n = 282 and Estonia n = 237). The age standardized incidence rate regarding total acute de novo leukaemias was slightly lower in Estonia than in Western Sweden (1.49/100,000 inhabitants/year for Estonia and 1.76 for Sweden, respectively), the difference being not statistically significant. However, the survival data for the two countries were highly different (P < 0.001). Thus, the relative survival for the total group of patients aged 16-64 years in Estonia at 1 year was 20.7% and at 5 years 3.6%, respectively. The corresponding figures for the Swedish patients were considerably higher, 65.2 and 29.4%, respectively. Further, the 5 year survival significantly (P < 0.05) increased for the Swedish patients over the 3 consecutive 5-year periods. No such improvement was recorded for the Estonian patients.