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Adverse psychological outcomes in long-term survivors of hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study (BMTSS)

Can-Lan Sun, Liton Francisco, K. Scott Baker, Daniel J. Weisdorf, Stephen J. Forman and Smita Bhatia

Article Figures & Data

Figures

  • Figure 1

    Magnitude of risk of poor psychological outcomes. Survivors were compared with siblings, adjusted for sex, age at study participation (continuous), race/ethnicity (non-Hispanic white, others), marital status (married, not married), income (< $20 000/y, $20 000-$60 000/y, > $60 000/y), education (did not complete high school (HS)/HS graduate, some college or higher), insurance status (yes, no), health status (poor/fair, good/excellent), and grade of chronic health conditions (none, grade 1 or 2, grade 3 or 4).

  • Figure 2

    Prevalence of HCT survivors with adverse psychosocial outcomes as a function of time from HCT. (A) Among all survivors by years after HCT. (B) Among autologous survivors only. (C) Among allogeneic survivors only.

Tables

  • Table 1

    Item content of the subscales constituting the Brief Symptom Inventory-18

    BSI-18 subscales/items
    Anxiety
        1. Nervousness or shaking inside
        2. Feeling tense or keyed up
        3. Suddenly scared for no reason
        4. Spells of terror or panic
        5. Feeling so restless you couldn't sit
        6. Feeling fearful
    Depression
        1. Feeling no interest in things
        2. Feeling lonely
        3. Feeling blue
        4. Feeling of worthlessness
        5. Feeling hopeless about the future
        6. Thoughts of ending your life
    Somatization
        1. Faintness or dizziness
        2. Pains in heart or chest
        3. Nausea or upset stomach
        4. Trouble getting your breath
        5. Numbness or tingling in parts of your body
        6. Feeling weak in parts of the body
    • BSI-18 indicates Brief Symptom Inventory-18.

  • Table 2

    Characteristics of HCT survivors and siblings

    CharacteristicSurvivors, no. (%), N = 1065Siblings, no. (%), N = 309P
    Male sex, %585 (54.9)113 (36.6)< .001
    Race: non-Hispanic white*825 (77.5)270 (88.0)< .001
    Did not complete HS/ HS graduate*222 (20.9)38 (12.3)< .001
    Household income, $< .001
        > 60 000/y438 (44.2)189 (64.3)
        20 000-60 000/y397 (40.1)93 (31.6)
        < 20 000/y155 (15.7)12 (4.1)
        No health insurance*88 (8.4)14 (4.6)0.03
    Chronic health condition< .001
        None386 (36.2)189 (61.2)
        Grade1/2492 (46.2)96 (31.0)
        Grade3/4187 (17.6)24 (7.8)
    Major categories of chronic health conditions
    Cardiovascular6.52.6.01
        Coronary artery disease1.71.6.93
        Congestive heart failure0.50.59
        Stroke1.30.3.21
    Auditory or visual2.51.0.12
        Legally blind or loss of an eye1.40.03
        Hearing loss not corrected by an aid1.11.01.00
    Gastrointestinal2.80.7.03
        Surgery (intestinal obstruction/ colostomy)1.30.05
        Rectal or anal fissure0.90.71.00
        Cirrhosis0.80.21
    Endocrine2.31.0.24
        Diabetes1.80.7.19
    Musculoskeletal problems3.30.7.01
        Joint replacement3.30.7.01
    Renal0.40.58
        Dialysis support0.40.58
    New malignancies2.42.9.54
    Median age at study participation, y (range)44 (18-73)45.2 (19-79).05
    Interval between HCT and study, y
        Median (range)7.4 (2-28)NA
        2-5 y328 (30.8)NA
        6-10 y397 (37.3)NA
        11+ y340 (31.9)NA
    Primary cancer diagnosis
        Aplastic anemia56 (5.3)NA
        Chronic myeloid leukemia249 (23.4)NA
        Acute myeloid leukemia255 (23.9)NA
        Hodgkin lymphoma92 (8.9)NA
        Non-Hodgkin lymphoma208 (19.5)NA
        Acute lymphoblastic leukemia106 (10.0)NA
        Multiple myeloma47 (4.4)NA
        Others52 (4.9)NA
    Stem cell donor
        Autologous HCT469 (44.0)NA
        Allogeneic, sibling donor497 (46.7)NA
        Allogeneic, unrelated donor99 (9.3)NA
    High risk of relapse at HCT*373 (35.1)NA
    Total body irradiation–based transplant regimens815 (76.7)NA
    Among allogeneic HCT survivors only, cGVHD
        No276 (46.4)NA
        Active cGVHD134 (22.5)NA
        Resolved cGVHD185 (31.1)NA
    Immune suppression
        Any immunosuppression576 (96.8)NA
        Methotrexate475 (80.0)NA
        Cyclosporine403 (67.7)NA
        Prednisone336 (56.6)NA
    • HCT indicates hematopoietic cell transplantation; HS, high school; NA, not applicable; and cGVHD, chronic GVHD.

    • * Two subjects with unknown race; 6 subjects with unknown education; 90 subjects with unknown household income; 18 subjects with unknown insurance status; and 3 patients with unknown risk of relapse status at HCT.

    • Key chronic health conditions within each category shown here. Some participants reported > 1 condition, and therefore the total number within each category does not total the sum of conditions show here. Percentages are based on the total number of participants who provided data for each variable, rather than on the total number of subjects in the cohort; percentages may not total 100 because of rounding.

    • Median (range), not no. (%).

  • Table 3

    Multivariate analysis of poor psychological outcomes: survivor and survivor subgroups compared with siblings

    AnxietyDepressionSomatic distressGlobal distress
    OR (95% CI)POR (95% CI)POR (95% CI)POR (95% CI)P
    Siblings1.001.001.001.00
    Survivors1.12 (0.47-2.67).801.15 (0.60-2.18).672.88 (1.44-5.76).0031.79 (0.81-3.93).15
    By primary cancer diagnosis
        Aplastic anemia0.72 (0.13-3.97).700.72 (0.21-2.52).612.06 (0.62-6.80).231.34 (0.35-5.16).67
        Chronic myeloid leukemia1.01 (0.36-2.79).991.34 (0.64-2.81).433.53 (1.65-7.55).0012.19 (0.92-5.24).08
        Acute myeloid leukemia1.14 (0.41-3.16).811.47 (0.70-3.06).313.25 (1.50-7.01).0031.88 (0.77-4.57).16
        Hodgkin lymphoma0.20 (0.02-1.75).140.21 (0.04-1.00).052.18 (0.82-5.81).120.53 (0.13-2.23).39
        Non-Hodgkin lymphoma1.64 (0.59-4.55).341.14 (0.51-2.58).752.77 (1.24-6.21).012.43 (0.97-6.08).06
        Acute lymphoblastic leukemia1.32 (0.40-4.37).651.52 (0.64-3.59).342.35 (0.91-6.08).081.53 (0.53-4.43).43
        Multiple myeloma1.06 (0.22-5.09).950.60 (0.14-2.53).494.45 (1.53-12.92).011.26 (0.31-5.19).75
        Others1.45 (0.28-7.53).660.96 (0.25-3.76).960.47 (0.06-3.90).491.16 (0.22-6.01).86
    By stem cell donor
        Autologous HCT1.01 (0.39-2.58).991.02 (0.51-2.06).952.60 (1.25-5.38).011.53 (0.66-3.55).32
        Allogeneic, sibling donor1.15 (0.45-2.92).781.34 (0.68-2.65).402.88 (1.38-6.02).001.96 (0.85-4.49).11
        Allogeneic, unrelated donor1.54 (0.48-4.90).470.91 (0.35-2.36).854.32 (1.84-10.18).0012.28 (0.83-6.21).11
    By risk of relapse at HCT
        Standard risk0.89 (0.32-2.44).821.15 (0.55-2.39).712.67 (1.22-5.84).011.75 (0.73-4.18).21
        High risk1.84 (0.64-5.29).261.17 (0.51-2.68).724.18 (1.79-9.74).0011.99 (0.76-5.24).16
    By transplant regimens
        Chemotherapy alone0.70 (0.16-3.11).640.75 (0.26-2.20).602.42 (0.87-6.79).090.90 (0.25-3.22).87
        Total body irradiation–based1.24 (0.47-3.24).661.23 (0.60-2.51).573.15 (1.46-6.76).0032.00 (0.85-4.70).11
    By cGVHD status (among allogeneic HCT survivors only)
        No1.17 (0.41-3.33).770.89 (0.40-1.99).782.32 (1.01-5.33).051.32 (0.51-3.41).56
        Active cGVHD1.96 (0.66-5.79).221.40 (0.60-3.25).445.14 (2.21-11.89)< .0013.04 (1.17-7.88).02
        Resolved cGVHD0.56 (0.16-1.99).371.34 (0.60-3.00).472.49 (1.04-5.97).041.61 (0.61-4.28).34
    By exposure to immunosuppressants (among allogeneic HCT survivors only)
        Use of any immunosuppression1.23 (0.47-3.19).681.20 (0.59-2.44).613.00 (1.40-6.43).0051.90 (0.81-4.44).14
        Methotrexate1.22 (0.46-0.00).691.06 (0.51-2.21).873.15 (1.46-6.79).081.75 (0.73-4.19).21
        Cyclosporine1.22 (0.46-3.26).691.46 (0.71-2.99).313.32 (1.54-7.15).0032.04 (0.86-4.85).11
        Prednisone1.63 (0.62-4.33).331.53 (0.74-3.18).253.76 (1.72-8.21).1062.46 (1.02-5.91).04
    • OR indicates odds ratio; CI, confidence interval; HCT, hematopoietic cell transplantation; and cGVHD, chronic GVHD.

  • Table 4

    Multivariate analysis of sociodemographic and clinical factors in relation to poor psychological outcomes among HCT survivors

    AnxietyDepressionSomatizationGlobal distress
    OR (95% CI)POR (95% CI)POR (95% CI)POR (95% CI)P
    Sex
        Female1.001.001.001.00
        Male1.02 (0.56-1.86).951.80 (1.14-2.85).010.89 (0.60-1.31).551.09 (0.68-1.76).71
    Race/ethnicity
        Non-Hispanic white1.001.001.001.00
        Others1.94 (0.98-3.87).061.28 (0.75-2.18).361.60 (0.99-2.60).052.04 (1.17-3.55).01
    Education
        Did not complete HS/HS graduate1.001.001.001.00
        Some college or above0.62 (0.31-1.21).160.64 (0.38-1.09).101.26 (0.75-2.11).380.81 (0.46-1.43).47
    Household income, $
        > 60 000/y1.001.001.001.00
        20 000-60 000/y3.28 (1.41-7.59).012.12 (1.21-3.71).011.92 (1.21-3.05).012.04 (1.11-3.74).02
        < 20 000/y3.22 (1.08-9.64).043.10 (1.56-6.19)< .0012.28 (1.23-4.24).012.54 (1.21-5.35).01
    Health insurance
        Yes1.001.001.001.00
        No0.87 (0.31-2.43).801.16 (0.59-2.32).661.20 (0.61-2.37).601.35 (0.66-2.78).42
    Marital status
        Married1.001.001.001.00
        No0.82 (0.42-1.59).551.45 (0.88-2.37).141.02 (0.65-1.57).951.28 (0.76-2.17).35
    Health status
        Excellent/good1.001.001.001.00
        Fair/poor3.80 (2.03-7.12)< .00013.56 (2.20-5.74)< .00015.58 (3.71-8.39)< .00015.98 (3.65-9.81)< .0001
    Chronic health condition
        None1.001.001.001.00
        Grade1/21.36 (0.68-2.73).391.48 (0.88-2.48).141.44 (0.91-2.28).121.21 (0.70-2.10).49
        Grade3/41.39 (0.57-3.38).471.49 (0.76-2.90).241.91 (1.09-3.36).021.37 (0.68-2.74).38
    Risk of relapse at HCT
        Standard risk1.001.001.001.00
        High risk1.18 (0.64-2.20).590.75 (0.46-1.21).230.95 (0.63-1.43).810.77 (0.46-1.28).31
    Age at HCT, year (per 10 y)0.91 (0.70-1.20).520.80 (0.66-0.98).030.98 (0.82-1.17).860.88 (0.71-1.09).25
    Time since HCT (per 10 y)0.62 (0.29-1.29).200.55 (0.32-0.93).030.56 (0.35-0.92).020.56 (0.31-0.99).05
    Primary cancer diagnosis
        CML1.001.001.001.00
        AML/ALL1.32 (0.60-2.92).491.19 (0.69-2.08).530.94 (0.57-1.54).790.92 (0.50-1.67).78
        HL/NHL0.99 (0.41-2.38).990.61 (0.31-1.19).140.68 (0.39-1.17).160.82 (0.42-1.60).56
        SAA/MM/others0.95 (0.33-2.69).920.59 (0.26-1.35).210.65 (0.33-1.29).220.65 (0.28-1.52).32
    Stem cell donor
        Autologous HCT1.001.001.001.00
        Allogeneic, sibling donor1.35 (0.67-2.71).401.41 (0.85-2.33).191.28 (0.82-2.01).281.41 (0.81-2.46).22
        Allogeneic, unrelated donor1.61 (0.61-4.26).340.82 (0.36-1.87).641.60 (0.86-2.96).141.42 (0.65-3.08).38
    Transplant regimens
        Chemotherapy alone1.001.001.001.00
        Total body irradiation–based1.63 (0.75-3.53).221.96 (1.06-3.63).031.63 (0.98-2.71).061.98 (1.03-3.80).04
    cGVHD (among allogeneic HCT survivors only)
        No1.001.001.001.00
        Active cGVHD1.69 (0.66-4.33).271.47 (0.69-3.14).322.00 (1.03-3.89).042.20 (1.01-4.79).05
        Resolved cGVHD0.44 (0.15-1.33).151.49 (0.76-2.93).250.99 (0.51-1.93).981.13 (0.53-2.41).75
    Any immunosuppression (among allogeneic HCT survivors only)
        Methotrexate1.50 (0.54-4.19).440.66 (0.33-1.31).231.31 (0.66-2.58).440.79 (0.38-1.64).53
        Cyclosporine0.97 (0.32-2.91).952.93 (1.15-7.49).021.00 (0.46-2.20)1.001.31 (0.53-3.27).56
        Prednisone2.62 (1.11-6.19).032.27 (1.24-4.18).011.80 (1.04-3.11).042.28 (1.19-4.36).01
    • Primary diagnosis, stem cell donor, transplant regimens, chronic GVHD, and use of immunosuppressants were included in the model one at a time. Adjusted for sex, age at study participation (continuous), race/ethnicity (non-Hispanic white, others), marital status (married, not married), income (< $20 000/y, 20 000-60 000/y, > 60 000/y), education (did not complete high school/high-school graduate, some college or above), insurance status (yes, no) and health status (poor/fair, good/excellent), grade of chronic health conditions (none, grade 1 or 2, grade 3 or 4).

    • HCT indicates hematopoietic cell transplantation; OR, odds ratio; CI, confidence interval; HS, high school; CML, chronic myeloid leukemia; AML, acute myeloid leukemia; ALL, acute lymphoid leukemia; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma; SAA, severe aplastic anemia; MM, multiple myeloma; and cGVHD, chronic GVHD.