Survivors Of Childhood non-Hodgkin Lymphoma Research Articles

Late outcomes of adult survivors of childhood non-Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study

Background Survivors of childhood non-Hodgkin lymphoma (NHL) are at increased risk for chronic health conditions. The objective of this study was to characterize health conditions, neurocognitive function, and physical performance among a clinically evaluated cohort of 200 childhood NHL survivors. Method Chronic health and neurocognitive conditions were graded as per a modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and impaired physical function defined as performance < 10th percentile of normative data. Multivariable regression was used to investigate associations between sociodemographic characteristics, therapeutic exposures, and outcomes. Results Survivors were a median age of 10 years (range 1–19) at diagnosis and 34 years (range 20–58) at evaluation. Eighty-eight (44%) received radiation, 46 (23%) cranial radiation, and 69 (35%) high-dose methotrexate. Most prevalent CTCAE Grades 3–4 (severe life-threatening) conditions were obesity (35%), hypertension (9%), and impairment of executive function (13%), attention (9%), and memory (4%). Many had impaired strength (48%), flexibility (39%), muscular endurance (36%), and mobility (36%). Demographic and treatment-related factors were associated with the development of individual chronic diseases and functional deficits. Conclusions Clinical evaluation identified a high prevalence of chronic health conditions, neurocognitive deficits, and performance limitations in childhood NHL survivors.

Neurocognitive, Psychosocial, and Quality of Life Outcomes in Adult Survivors of Childhood Non-Hodgkin Lymphoma in the St. Jude Lifetime (SJLIFE) Cohort

Introduction: Survivors of childhood cancer are at risk for neurocognitive impairment. The pattern and degree of such impairment in childhood non-Hodgkin lymphoma (NHL) survivors has not been previously assessed.Methods: Adult survivors of childhood NHL participating in the SJLIFE Cohort Study, ≥10 years from diagnosis, and ≥18 years old were recruited for neurocognitive testing, with age-adjusted z-scores compared to community controls and normative data. Cumulative treatment exposures were abstracted from medical records. Multivariable modeling, adjusting for age, gender, and time from diagnosis, was used to calculate relative risks (RR) and 95% confidence intervals (CI).Results: 187 NHL survivors (59% of eligible) completed neurocognitive testing. Survivors were a median [range] age at diagnosis of 10 [2 - 21] years, median time from diagnosis 26 [11 - 48] years, and median age at evaluation 35 [19 - 58] years. Fifty-six (30%) received cranial radiation (CRT), 70 (37%) high-dose methotrexate (HD-MTX), 40 (21%) high-dose cytarabine (HD-ARAC), and 151 (81%) intrathecal (IT) chemotherapy. Survivors had full scale intelligence (mean = -0.1, SD = 1.0, range: -2.7 - 2.0), memory (mean= -0.2, SD = 1.0, range: -4.2 - 1.6), and attention (mean = 0, SD = 0.7, range: -2.5 - 1.4) within normal limits. Survivors demonstrated worse executive function, processing speed, and academics compared to community controls and normative data (Table 1). In multivariable models, there were no statistically significant associations with worse academics, processing speed, executive function and behavior rating and CRT, HD-MTX, HD-ARAC, or IT chemotherapy. Survivors reported more depression and somatization compared to community controls (p's < 0.001) and normative data (p's < 0.01). CRT (p = 0.003) was associated with improved somatization while longer time from diagnosis (p = 0.01) was associated with worse somatization. Survivors reported worse emotional quality of life compared to community controls (p = 0.005) and normative data (p < 0.001). Following adjustment for neurocognitive impairment, self-reported neurobehavioral problems (shift and emotional control) were associated with worse emotional quality of life (vitality, social functioning, mental health) (p's < 0.001). There was no statistically significant difference between survivors and controls for educational attainment and full time employment. Survivors with worse academic (RR = 1.5, 95% CI: 1.2 - 1.7) and executive function (RR = 1.1, 95% CI: 1.0 - 1.2) were more likely to not graduate from college. Those with lower processing speed were more likely to be unemployed or work only part time (RR = 1.3, 95% CI: 1.1 - 1.4).Conclusions: Adult survivors of childhood NHL experience impaired neurocognitive function, mental health, and quality of life, which at 26 years post-diagnosis is not related to original treatment exposures. Associations between impairment and chronic health conditions should be explored. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Late outcomes among adult survivors of childhood non-Hodgkin lymphoma (NHL): A report from the St. Jude Lifetime Cohort Study.

10064 Background: Adult survivors of childhood NHL are at risk for chronic conditions likely underestimated by patient reported outcomes. Prevalence and severity based on direct clinical assessment are lacking. Methods: Clinical, laboratory, and performance-based evaluations were obtained on 200 adult survivors of pediatric NHL at St. Jude Children’s Research Hospital. Chronic conditions were graded per CTCAE criteria. Impaired physical function was defined as performance below the 10th percentile of normative data. Multivariable Poisson regression models were used to investigate associations [relative risk (RR), 95% confidence intervals (CI)] between patient characteristics, therapies, and clinical outcomes. Results: Survivors (66% male, 87% white) were a median age of 10 years (range 1-19) at diagnosis and 34 years (20-58) at evaluation. Forty-six (23%) received radiation to the brain, 69(35%) high dose methotrexate, and 161(81%) steroids. Most (93%) had ≥ 1 chronic condition, 77% ≥ 2 chronic conditions...

Endocrine late sequelae in long-term survivors of childhood non-Hodgkin lymphoma

Aim of this study was to investigate the long-term endocrine effects of treatment of childhood non-Hodgkin lymphoma (NHL). A single-center cohort of 84 survivors (22 females) was included in this retrospective study. Median age was 21 years (9-40 years) and time after cessation of therapy 12 years (4-30 years). Height, weight, percentage fat, lean body mass (LBM), bone mineral content (BMC), bone mineral density of total body (BMD(TB)) and bone mineral density of lumbar spine (BMD(LS)) were measured. Thyroid-stimulating hormone (TSH), free thyroxin (fT4), insulin-like growth factor-1 (IGF-1), inhibin B and anti-müllerian hormone (AMH) levels were measured. Results were compared with Dutch controls. Height was lower in survivors [mean standard deviation score (SDS) -0.36, P = 0.002], but further analysis showed that shorter stature was already present at diagnosis (mean SDS -0.28, P = 0.023). Body mass index, percentage fat, BMC, BMD(TB) and BMD(LS) were not different from controls. LBM was lower in survivors (mean SDS -0.47, P = 0.008). TSH, fT4 and IGF-1 were normal in all survivors. Three of 20 adult females had low AMH levels and 23 of 42 adult males had low inhibin B levels. Twelve years after cessation of treatment, NHL survivors did not develop adiposity, osteoporosis or thyroid disease. Male survivors may be at risk for infertility.

Endocrine Late Sequelae in Long-Term Survivors of Childhood Non-Hodgkin Lymphoma

Abstract 5215 Introduction.Currently, the 5-year survival for childhood NHL is ∼80%. Because of this high survival rate and since treatment is administered in a growing and developing individual, long-term side effects are an important issue. Studies on endocrine long-term effects in survivors of childhood non-Hodgkin lymphoma (NHL) are scarce and often limited by small sample sizes, or by the fact that data of NHL survivors have been combined with that of survivors of other malignancies. Aim of this study was to investigate the long-term endocrine effects of treatment for childhood NHL. Methods.A single centre cohort of 84 survivors (22 females) was included in this retrospective study. Median age was 21 yrs (9–40 yrs) and time after cessation of therapy 12 yrs (4–30 yrs). Height, weight, percentage fat, lean body mass (LBM), bone mineral content (BMC), bone mineral density of total body (BMDTB) and lumbar spine (BMDLS) were measured. Bone mineral apparent density of the lumbar spine (BMADLS) was calculated to correct for bone size. Thyroid stimulating hormone (TSH), free thyroxin (fT4), insulin-like growth factor-1 (IGF-1), Inhibin-B and anti-müllerian hormone (AMH) levels were measured. Results were compared with Dutch controls. Results.Height was lower in survivors at follow-up (mean SDS −0.36, P=0.002), but further analysis showed that shorter stature was already present at diagnosis (mean SDS −0.28, P=0.023). BMI, percentage fat, BMC, BMDTB, BMDLS and BMADLS were not different from controls. LBM was lower in survivors (mean SDS −0.47, P=0.008). TSH, fT4 and IGF-1 were normal in all survivors. Three out of 20 adult females had low AMH levels and 55% (23/42) of adult males had low Inhibin-B levels. Conclusion.Twelve years after cessation of therapy, survivors of NHL did not develope adiposity, osteopenia or osteoporosis or thyroid disease. Male NHL survivors seem to be at risk for infertility. Disclosures:No relevant conflicts of interest to declare.

Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study

AbstractSecond primary malignancies and premature death are a concern for patients surviving treatment for childhood lymphomas. We assessed mortality and second malignant neoplasms (SMNs) among 1082 5-year survivors of non-Hodgkin lymphoma (NHL) in the Childhood Cancer Survivor Study, a multi-institutional North American retrospective cohort study of cancer survivors diagnosed from 1970 to 1986. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated using US population rates. Relative risks for death and solid tumor SMNs were calculated based on demographic, clinical, and treatment characteristics using Poisson regression models. There were 87 observed deaths (SMR = 4.2; 95% CI, 1.8-4.1) with elevated rates of death from solid tumors, leukemia, cardiac disease, and pneumonia. Risk for death remained elevated beyond 20 years after NHL. Risk factors for death from causes other than NHL included female sex (rate ratio [RR] = 3.4) and cardiac radiation therapy exposure (RR = 1.9). There were 27 solid tumor SMNs (SIR = 3.9; 95% CI, 2.6-5.7) with 3% cumulative incidence between 5 and 20 years after NHL diagnosis. Risk factors were female sex (RR = 3.1), mediastinal NHL disease (RR = 5.2), and breast irradiation (RR = 4.3). Survivors of childhood NHL, particularly those treated with chest RT, are at continued increased risk of early mortality and solid tumor SMNs.

Cause-Specific Mortality and Second Cancer Incidence after Non-Hodgkin Lymphoma: A Report from the Childhood Cancer Survivor Study.

Background: Second primary malignancies and premature death are a concern for patients surviving treatment for childhood lymphomas. Despite in-depth reports on second cancer risk after Hodgkin lymphoma, there is limited published information on clinical, demographic, and treatment risk factors for second malignant neoplasms (SMNs) or deaths after non-Hodgkin lymphoma (NHL).Methods: We assessed mortality and SMNs among 1,082 five-year survivors of NHL in the Childhood Cancer Survivor Study, a multi-institutional North American retrospective cohort study of pediatric cancer survivors diagnosed between 1970 and 1986 before age 21. We searched the National Death Index for dates and causes of death and inquired about SMNs in periodic questionnaires, with confirmation of all reported SMNs by a study pathologist. We calculated standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) based on United States population rates. We calculated relative risks (RRs) for death and SMNs by demographic, clinical, and treatment characteristics using proportional hazards modeling. Medical physicists determined organ exposure to radiation therapy (RT) based on clinical RT records.Results: There were 87 deaths among 5-year survivors (SMR=4.2, 95% confidence interval (CI): 1.8, 4.1). Leading causes of death were NHL (n=21), solid tumors (n=17), circulatory diseases (n=12), and leukemia (n=10). There were elevated rates of mortality due to NHL, solid tumor SMNs, leukemia, cardiac disease, and pneumonia. The mortality rate remained elevated beyond 20 years after NHL. Risk factors for death included NHL relapse (RR=8.5), doxorubicin (RR=1.8), bleomycin (RR=4.1), platinum agents (RR=4.0), and cardiac RT exposure (RR=1.8). There were 31 SMNs, including 27 solid tumor SMNs (SIR=3.9, 95%.CI: 2.6, 5.7), specifically SMNs of the breast (n=6, SIR=9.1), thyroid (n=6, SIR=9.4), oral cavity and pharynx (n=3), brain and nervous system (n=3), bone (n=2) and urinary bladder (n=2). Risk factors for solid tumor SMNs were female sex (RR=3.1), mediastinal NHL disease (RR=5.2), and breast RT exposure (RR=4.3). Overall cumulative incidence of solid tumor SMNs from 5 to 20 years after NHL diagnosis was 0.03 (95% CI: 0.02, 0.05).Conclusions: We identified a four-fold risk of mortality and three-fold risk of SMNs in a large cohort of pediatric NHL survivors relative to the general U.S. population. Survivors of childhood NHL, particularly those treated with chest RT, may be at continued increased risk of early mortality and solid tumor SMNs. Health care providers responsible for this population should remain alert to second cancers and other severe late health outcomes.