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  1. Article ; Online: Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia.

    Hisada, Yohei / Archibald, Sierra J / Bansal, Karan / Chen, Yanjun / Dai, Chen / Dwarampudi, Sindhu / Balas, Nora / Hageman, Lindsey / Key, Nigel S / Bhatia, Smita / Bhatia, Ravi / Mackman, Nigel / Gangaraju, Radhika

    Journal of thrombosis and haemostasis : JTH

    2024  

    Abstract: Background: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.: Objectives: ...

    Abstract Background: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.
    Objectives: To evaluate the associations between biomarker levels and bleeding and DVT in acute leukemia patients.
    Methods: We examined plasma levels of activators, inhibitors, and biomarkers of the coagulation and fibrinolytic pathways in patients aged ≥18 years with newly diagnosed acute leukemia compared with those of normal controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and DVT in acute leukemia patients. The study included 358 patients with acute leukemia (29 with acute promyelocytic leukemia [APL], 253 with non-APL acute myeloid leukemia, and 76 with acute lymphoblastic leukemia) and 30 normal controls.
    Results: Patients with acute leukemia had higher levels of extracellular vesicle tissue factor (EVTF) activity, phosphatidylserine-positive extracellular vesicles, plasminogen activator inhibitor-1, plasmin-antiplasmin complexes, and cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared with normal controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among acute leukemia patients. There were 41 bleeding and 23 DVT events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (subdistribution hazard ratio, 2.30; 95% CI, 0.99-5.31), whereas high levels of plasminogen activator inhibitor-1 were associated with increased risk of DVT (subdistribution hazard ratio, 3.00; 95% CI, 0.95-9.47) in these patients.
    Conclusion: Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and DVT.
    Language English
    Publishing date 2024-04-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1016/j.jtha.2024.03.020
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    Zs.A 5805: Show issues Location:
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  2. Article ; Online: Body composition and late-occurring chronic health conditions after autologous stem cell transplantation for lymphoma.

    Giri, Smith / Harmon, Christian / Landier, Wendy / Chen, Yanjun / Wu, Jessica / Hageman, Lindsey / Balas, Nora / Francisco, Liton / Bosworth, Alysia / Weisdorf, Daniel J / Forman, Stephen J / Armenian, Saro H / Williams, Grant R / Bhatia, Smita

    Cancer

    2024  

    Abstract: Background: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition ...

    Abstract Background: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT.
    Methods: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders.
    Results: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM.
    Conclusions: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.35298
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  3. Article ; Online: Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms After Autologous Transplant for Hodgkin Lymphoma.

    Yan, Chengcheng / Richard, Melissa A / Gibson, Christopher J / He, Jianbo / Bosworth, Alysia / Crossman, David K / Singh, Purnima / Hageman, Lindsey / Kalra, Rashi / Armenian, Saro H / Vose, Julie / Weisdorf, Daniel J / Ebert, Benjamin L / Yasui, Yutaka / Forman, Stephen J / Bhatia, Ravi / Bhatia, Smita

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2024  , Page(s) JCO2302547

    Abstract: Purpose: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for Hodgkin lymphoma (HL). Although previous studies have reported an association between clonal ... ...

    Abstract Purpose: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for Hodgkin lymphoma (HL). Although previous studies have reported an association between clonal hematopoiesis (CH) in the infused PBSC product and subsequent post-aPBSCT risk of t-MN in patients with non-HL, information about patients with HL treated with aPBSCT is not available.
    Methods: We constructed a retrospective cohort of 321 patients with HL transplanted at a median age of 34 years (range, 18-71). Targeted DNA sequencing of PBSC products performed for CH-associated or myeloid malignancy-associated genes identified pathogenic mutations in these patients.
    Results: CH was identified in the PBSC product of 46 patients (14.3%) with most prominent representation of
    Conclusion: The presence of
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.23.02547
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  4. Article ; Online: Pre-frailty after blood or marrow transplantation and the risk of subsequent mortality.

    Balas, Nora / Richman, Joshua S / Landier, Wendy / Shrestha, Sadeep / Bruxvoort, Katia J / Hageman, Lindsey / Meng, Qingrui / Ross, Elizabeth / Bosworth, Alysia / Wong, F Lennie / Bhatia, Ravi / Forman, Stephen J / Armenian, Saro H / Weisdorf, Daniel J / Bhatia, Smita

    Leukemia

    2024  

    Abstract: We examined the prevalence, risk factors, and association between pre-frailty and subsequent mortality after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 3346 individuals who ... ...

    Abstract We examined the prevalence, risk factors, and association between pre-frailty and subsequent mortality after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 3346 individuals who underwent BMT between 1974 and 2014 at one of three transplant centers and survived ≥2 years post-BMT. Participants completed the BMTSS survey at a median of 9 years from BMT and were followed for subsequent mortality for a median of 5 years after survey completion. Closest-age and same-sex biological siblings also completed the survey. Previously published self-reported indices (exhaustion, weakness, low energy expenditure, slowness, unintentional weight loss) classified participants as non-frail (0-1 indices) or pre-frail (2 indices). National Death Index was used to determine vital status and cause of death. Overall, 626 (18.7%) BMT survivors were pre-frail. BMT survivors had a 3.2-fold higher odds of being pre-frail (95% CI = 1.9-5.3) compared to siblings. Compared to non-frail survivors, pre-frail survivors had higher hazards of all-cause mortality (adjusted hazard ratio [aHR] = 1.6, 95% CI = 1.4-2.0). Female sex, pre-BMT radiation, smoking, lack of exercise, anxiety, and severe/life-threatening chronic health conditions were associated with pre-frailty. The novel association between pre-frailty and subsequent mortality provides evidence for interventions as pre-frail individuals may transition back to their robust state.
    Language English
    Publishing date 2024-04-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-024-02238-2
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  5. Article ; Online: Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults-a BMTSS report.

    Holmqvist, Anna Sällfors / Meng, Qingrui / Dai, Chen / Hageman, Lindsey / Landier, Wendy / Wu, Jessica / Francisco, Liton F / Ross, Elizabeth Schlichting / Balas, Nora / Bosworth, Alysia / Te, Hok Sreng / Bhatia, Ravi / Rosenthal, Joseph / Wong, F Lennie / Weisdorf, Daniel / Armenian, Saro H / Bhatia, Smita

    Leukemia

    2024  Volume 38, Issue 3, Page(s) 601–609

    Abstract: We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL  ...

    Abstract We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3-4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3-5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0-40.0) and median follow-up was 9.8 years (2.0-32.1). Survivors were at a 3-fold higher adjusted odds for grade 3-4 conditions (95% CI = 2.3-4.1) vs. comparison subjects. Factors associated with grade 3-5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27-4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13-2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34-0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up.
    MeSH term(s) Child ; Humans ; Adolescent ; Young Adult ; Adult ; Bone Marrow Transplantation/adverse effects ; Bone Marrow ; Neoplasm Recurrence, Local ; Lymphoma/therapy ; Transplantation, Autologous/adverse effects ; Morbidity
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-024-02144-7
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  6. Article ; Online: Feasibility of implementing a supervised telehealth exercise intervention in frail survivors of hematopoietic cell transplantation: a pilot randomized trial.

    Lee, Kyuwan / Shamunee, Justin / Lindenfeld, Lanie / Ross, Elizabeth / Hageman, Lindsey / Sedrak, Mina S / Wong, F Lennie / Nakamura, Ryotaro / Forman, Stephen J / Bhatia, Smita / Armenian, Saro H

    BMC cancer

    2023  Volume 23, Issue 1, Page(s) 390

    Abstract: Background: Patients undergoing hematopoietic cell transplantation (HCT) are at high risk of chronic health complications, including frailty and physical dysfunction. Conventional exercise programs have been shown to improve frailty in other cancer ... ...

    Abstract Background: Patients undergoing hematopoietic cell transplantation (HCT) are at high risk of chronic health complications, including frailty and physical dysfunction. Conventional exercise programs have been shown to improve frailty in other cancer populations, but these have largely been based out of rehabilitation facilities that may act as geographic and logistical barriers. There is a paucity of information on the feasibility of implementing telehealth exercise interventions in long-term HCT survivors.
    Methods: We conducted a pilot randomized trial to assess the feasibility of an 8-week telehealth exercise intervention in 20 pre-frail or frail HCT survivors. Participants were randomized to either a telehealth exercise (N = 10) or delayed control (N = 10). We administered a remote physical function assessment at baseline, followed by an 8-week telehealth exercise intervention (30-60 min/session, 3 sessions/week), and post-intervention. The primary endpoint was feasibility as determined by 1) > 70% of participants completing all remote physical functional assessments, and 2) > 70% of participants in the exercise group completing > 70% (17/24) of the prescribed exercise sessions. Exploratory outcomes included changes in gait speed, handgrip strength, and short physical performance battery.
    Results: The mean [standard deviation] age at study enrollment was 64.7 [9.1] years old. Twelve had undergone allogenic and 8 had undergone autologous HCT at an average of 17 years from study enrollment. Both feasibility criteria were achieved. Nineteen patients (95%) completed all remote study outcome assessments at baseline and post-intervention, and nine participants in the exercise group completed > 70% of prescribed exercise sessions. Overall, no significant group x time interaction was observed on handgrip strength, fatigue, body mass index, and short physical performance battery test (P < 0.05). However, there were significant within-group improvements in four-meter gait speed (+ 13.9%; P = 0.004) and 5-minute gait speed (+ 25.4%; P = 0.04) in the exercise group whereas non-significant changes in four-meter gait speed (-3.8%) and 5-minute gait speed (-5.8%) were observed after 8 weeks.
    Conclusion: Implementing an 8-week telehealth exercise intervention for long-term HCT survivors was feasible. Our findings set the stage for innovative delivery of supervised exercise intervention that reduces the burden of frailty in HCT survivors as well as other at-risk cancer survivors.
    Trial registration: The protocol and informed consent were approved by the institutional IRB (IRB#20731) and registered (ClinicalTrials.gov NCT04968119; date of registration: 20/07/2021).
    MeSH term(s) Humans ; Aged ; Child ; Frailty ; Frail Elderly ; Hand Strength ; Feasibility Studies ; Pilot Projects ; Exercise Therapy/methods ; Survivors ; Hematopoietic Stem Cell Transplantation ; Telemedicine
    Language English
    Publishing date 2023-05-01
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2041352-X
    ISSN 1471-2407 ; 1471-2407
    ISSN (online) 1471-2407
    ISSN 1471-2407
    DOI 10.1186/s12885-023-10884-5
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  7. Article ; Online: Poverty and relapse risk in children with acute lymphoblastic leukemia: a Children's Oncology Group study AALL03N1 report.

    Wadhwa, Aman / Chen, Yanjun / Hageman, Lindsey / Hoppmann, Anna / Angiolillo, Anne / Dickens, David S / Neglia, Joseph P / Ravindranath, Yaddanapudi / Ritchey, A Kim / Termuhlen, Amanda / Wong, F Lennie / Landier, Wendy / Bhatia, Smita

    Blood

    2023  Volume 142, Issue 3, Page(s) 221–229

    Abstract: The association between individual-level poverty and relapse in children receiving maintenance treatment for acute lymphoblastic leukemia (ALL) remains unclear. In a secondary analysis of COG-AALL03N1, we used data from US Census Bureau to categorize ... ...

    Abstract The association between individual-level poverty and relapse in children receiving maintenance treatment for acute lymphoblastic leukemia (ALL) remains unclear. In a secondary analysis of COG-AALL03N1, we used data from US Census Bureau to categorize patients living below year-specific federal poverty thresholds, calculated using self-reported annual household income and size of household. Participants with federal poverty thresholds above 120% of their yearly household income were categorized as living in extreme poverty. Hazard of relapse was estimated using multivariable proportional subdistributional hazards regression for patients living in extreme poverty while receiving ALL maintenance therapy after adjusting for relevant predictors. Among 592 patients in this analysis, 12.3% of the patients were living in extreme poverty. After a median follow-up of 7.9 years, the cumulative incidence of relapse at 3 years from study enrollment among those living in extreme poverty was significantly higher (14.3%) than those not living in extreme poverty (7.6%). Multivariable analysis demonstrated that children living in extreme poverty had a 1.95-fold greater hazard of relapse than those not living in extreme poverty; this association was mitigated after the inclusion of race/ethnicity in the model, likely because of collinearity between race/ethnicity and poverty. A greater proportion of children living in extreme poverty were nonadherent to mercaptopurine (57.1% vs 40.9%); however, poor adherence did not completely explain the association between poverty and relapse risk. Future studies need to understand the mechanisms underlying the association between extreme poverty and relapse risk. This trial was registered at www.clinicaltrials.gov as #NCT00268528.
    MeSH term(s) Humans ; Child ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology ; Mercaptopurine ; Recurrence ; Poverty ; Incidence
    Chemical Substances Mercaptopurine (E7WED276I5)
    Language English
    Publishing date 2023-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023019631
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  8. Article: Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia.

    Hisada, Yohei / Archibald, Sierra J / Bansal, Karan / Chen, Yanjun / Dai, Chen / Dwarampudi, Sindhu / Balas, Nora / Hageman, Lindsey / Key, Nigel S / Bhatia, Smita / Bhatia, Ravi / Mackman, Nigel / Gangaraju, Radhika

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Background: Coagulopathy and associated bleeding and venous thromboembolism (VTE) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.: Objectives! ...

    Abstract Background: Coagulopathy and associated bleeding and venous thromboembolism (VTE) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.
    Objectives: To evaluate the associations between biomarker levels and bleeding and VTE in acute leukemia patients.
    Patients/method: We examined plasma levels of activators, inhibitors and biomarkers of the coagulation and fibrinolytic pathways in patients ≥18 years with newly diagnosed acute leukemia compared to healthy controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and VTE in acute leukemia patients. The study included 358 patients with acute leukemia (29 acute promyelocytic leukemia [APL], 253 non-APL acute myeloid leukemia [AML] and 76 acute lymphoblastic leukemia [ALL]), and 30 healthy controls.
    Results: Patients with acute leukemia had higher levels of extracellular vesicle (EV) tissue factor (TF) activity, phosphatidylserine-positive EVs, plasminogen activator inhibitor-1 (PAI-1), plasmin-antiplasmin complexes, cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared to healthy controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among the acute leukemia patients. There were 41 bleeding and 37 VTE events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (sHR 2.30, 95%CI 0.99-5.31) whereas high PAI-1 was associated with increased risk of VTE (sHR 3.79, 95%CI 1.40-10.28) in these patients.
    Conclusions: Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and VTE.
    Language English
    Publishing date 2023-10-19
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.18.23297216
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  9. Article ; Online: Individual prediction of nonadherence to oral mercaptopurine in children with acute lymphoblastic leukemia: Results from COG AALL03N1.

    Hoppmann, Anna L / Chen, Yanjun / Landier, Wendy / Hageman, Lindsey / Evans, William E / Wong, F Lennie / Relling, Mary V / Bhatia, Smita

    Cancer

    2021  Volume 127, Issue 20, Page(s) 3832–3839

    Abstract: Background: Poor mercaptopurine (6MP) adherence (mean adherence rate < 90%) increases the relapse risk among children with acute lymphoblastic leukemia (ALL). 6MP adherence remains difficult to measure in real time. Easily measured patient-level factors ...

    Abstract Background: Poor mercaptopurine (6MP) adherence (mean adherence rate < 90%) increases the relapse risk among children with acute lymphoblastic leukemia (ALL). 6MP adherence remains difficult to measure in real time. Easily measured patient-level factors could identify patients at risk for poor adherence.
    Methods: The authors measured 6MP adherence via electronic monitoring for 6 months per patient. Using data from month 3, they created a risk prediction model for 6MP nonadherence in 407 children with ALL (mean age, 7.7 ± 4.4 years); they used receiver operating characteristic analyses in the training set (n = 250) and replicated this in the test set (n = 157).
    Results: Age, race/ethnicity, 6MP dose intensity, absolute neutrophil count, 6MP ingestion patterns, and household structure were retained in the prediction model. The model yielded areas under the receiver operating characteristic curve (AUCs) of 0.79 (95% confidence interval [CI], 0.71-0.85) and 0.74 (95% CI, 0.63-0.85) in the training and test sets, respectively. The model performed better for those who were ≥12 years old (AUC, 0.79; 95% CI, 0.59-0.99) than those <12 years old (AUC, 0.70; 95% CI, 0.58-0.81). Using the predicted probability of nonadherence based on receiver operating characteristic analysis, the authors developed a binary risk classifier to classify patients with a high or low probability of nonadherence. The sensitivity and specificity of the binary risk classifier were 71% and 76%, respectively. Adjusted for clinical prognosticators, the risk of relapse was 2.2-fold higher (95% CI, 0.94-5.1; P = .07) among patients with a high probability of nonadherence in comparison with those with a low probability, as identified by the risk prediction model.
    Conclusions: The risk prediction model identified patients with a high probability of nonadherence and could be used in real time to personalize recommendations and interventions in the clinic.
    Lay summary: The vast majority of children with acute lymphoblastic leukemia, the most common childhood cancer, are cured. The treatment of acute lymphoblastic leukemia includes taking an oral chemotherapy medicine (mercaptopurine) for approximately 2 years. Children who miss doses of this medicine (specifically children who take the medicine less than 90% of the time that it is prescribed) are more likely to suffer leukemia relapse. The authors of this article have measured mercaptopurine adherence with electronic bottle caps to determine characteristics of patients that predict nonadherence, and they have created a prediction tool that could allow physicians to identify and intervene with patients at high risk of nonadherence.
    MeSH term(s) Administration, Oral ; Area Under Curve ; Child ; Child, Preschool ; Humans ; Mercaptopurine/adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Recurrence
    Chemical Substances Mercaptopurine (E7WED276I5)
    Language English
    Publishing date 2021-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.33760
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  10. Article ; Online: Malignant Neoplasms of the Gastrointestinal Tract After Blood or Marrow Transplant.

    McDonald, Andrew / Dai, Chen / Meng, Qingrui / Hageman, Lindsey / Richman, Joshua / Wu, Jessica / Francisco, Liton / Ross, Elizabeth / Balas, Nora / Bosworth, Alysia / Te, Hok Sreng / Wong, F Lennie / Landier, Wendy / Salzman, Donna / Bhatia, Ravi / Weisdorf, Daniel J / Forman, Stephen J / Armenian, Saro H / Bhatia, Smita

    JAMA oncology

    2023  Volume 9, Issue 3, Page(s) 376–385

    Abstract: Importance: Survivors of blood or marrow transplant (BMT) are at increased risk of subsequent malignant neoplasms (SMNs). Cancers of the gastrointestinal (GI) system are of special interest because their clinical behavior is often aggressive, ... ...

    Abstract Importance: Survivors of blood or marrow transplant (BMT) are at increased risk of subsequent malignant neoplasms (SMNs). Cancers of the gastrointestinal (GI) system are of special interest because their clinical behavior is often aggressive, necessitating early detection by increasing awareness of high-risk populations.
    Objective: To describe the risk of SMNs in the GI tract after BMT.
    Design, setting, and participants: A cohort study of 6710 individuals who lived at least 2 years after BMT performed between January 1, 1974, and December 31, 2014, at City of Hope, University of Minnesota, or University of Alabama at Birmingham. End of follow-up was March 23, 2020. Data analysis was performed between September 1, 2022, and September 30, 2022.
    Exposures: Demographic and clinical factors; therapeutic exposures before or as part of BMT.
    Main outcomes and measures: Development of SMNs in the GI tract after BMT. Participants self-reported SMNs in the GI tract; these were confirmed with pathology reports, medical records, or both. For deceased patients, death records were used. Standardized incidence ratios determined excess risk of SMNs in the GI tract compared with that of the general population. Fine-Gray proportional subdistribution hazard models assessed the association between risk factors and SMNs in the GI tract.
    Results: The cohort of 6710 individuals included 3444 (51.3%) autologous and 3266 (48.7%) allogeneic BMT recipients. A total of 3917 individuals (58.4%) were male, and the median age at BMT was 46 years (range, 0-78 years). After 62 479 person-years of follow-up, 148 patients developed SMNs in the GI tract. The standardized incidence ratios for developing specific SMNs ranged from 2.1 for colorectal cancer (95% CI, 1.6-2.8; P < .001) to 7.8 for esophageal cancer (95% CI, 5.0-11.6; P < .001). Exposure to cytarabine for conditioning (subdistribution hazard ratio [SHR], 3.1; 95% CI, 1.5-6.6) was associated with subsequent colorectal cancer. Compared with autologous BMT recipients, allogeneic BMT recipients with chronic graft-vs-host disease were at increased risk for esophageal cancer (SHR, 9.9; 95% CI, 3.2-30.5). Conditioning with etoposide (SHR, 2.0; 95% CI, 1.1-3.5) and pre-BMT anthracycline exposure (SHR, 5.4; 95% CI, 1.3-23.4) were associated with an increased risk of liver cancer compared with no exposure to the respective agents.
    Conclusions and relevance: The findings of this cohort study are relevant for oncologists and nononcologists who care for the growing number of survivors of transplant. Awareness of subgroups of survivors of BMT at high risk for specific types of SMNs in the GI tract may influence recommendations regarding modifiable risk factors, as well as individualized screening.
    MeSH term(s) Humans ; Male ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Female ; Cohort Studies ; Bone Marrow ; Bone Marrow Transplantation/adverse effects ; Neoplasms/etiology ; Colorectal Neoplasms/etiology ; Esophageal Neoplasms ; Incidence
    Language English
    Publishing date 2023-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2022.6569
    Database MEDical Literature Analysis and Retrieval System OnLINE

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