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High probability of follow-up termination among AYA survivors after allogeneic hematopoietic cell transplantation

Koichi Miyamura, Takuya Yamashita, Yoshiko Atsuta, Tatsuo Ichinohe, Koji Kato, Naoyuki Uchida, Takahiro Fukuda, Kazuteru Ohashi, Hiroyasu Ogawa, Tetsuya Eto, Masami Inoue, Satoshi Takahashi, Takehiko Mori, Heiwa Kanamori, Hiromasa Yabe, Asahito Hama, Shinichiro Okamoto and Yoshihiro Inamoto

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  • Table 1.

    Patient characteristics

    CharacteristicNo. (%)
    Total number of patients17 980
    Patient age at transplantation (range), y34 (0-76)
     <153918 (22)
     15-293922 (22)
     30-392911 (16)
     40-493098 (17)
     ≥504131 (23)
    Patient sex
     Male10 248 (57)
     Female7732 (43)
    Diagnosis
     AML5789 (32)
     ALL4077 (23)
     Lymphoma/CLL1782 (10)
     CML1678 (9)
     MDS1663 (9)
     ATL440 (2)
     MPN322 (2)
     Plasma cell neoplasms243 (1)
     Aplastic anemia1322 (7)
     Immunodeficiency306 (2)
     Bone marrow failure182 (1)
     Inborn metabolic disorders176 (1)
    Disease risk
     Standard10 547 (59)
     High5447 (30)
     Nonmalignant1986 (11)
    Conditioning
     Myeloablative11 198 (62)
     Reduced intensity5184 (29)
     Unknown intensity1598 (9)
    Donor type
     Related bone marrow5061 (28)
     Related mobilized blood cells2509 (14)
     Unrelated bone marrow7241 (40)
     Unrelated mobilized blood cells18 (<1)
     Cord blood2845 (16)
     Haploidentical related306 (2)
    HLA matching*
     Match10 909 (74)
     Mismatch3920 (26)
    Year of transplantation
     1974-19993613 (20)
     2000-20055260 (29)
     2006-20139107 (51)
    Maximum grade of acute GVHD
     Grade 0-I11 903 (66)
     Grade II4528 (25)
     Grade III-IV1549 (9)
    Chronic GVHD before 2 y
     None10 228 (57)
     Limited3419 (19)
     Extensive4333 (24)
    • AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; ATL, adult T-cell leukemia/lymphoma; CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm.

    • * Cord blood and haploidentical transplantation are excluded.

  • Table 2.

    Factors associated with follow-up termination

    FactorUnivariateMultivariate
    HR (95% CI)PHR (95% CI)P
    Patient age (up to 16 y after HCT), y*
     <150.65 (0.60-0.70)<.0010.60 (0.56-0.66)<.001
     15-291.00 (reference)1.00 (reference)
     30-390.86 (0.79-0.94).0010.89 (0.82-0.97).011
     ≥400.74 (0.68-0.79)<.0010.79 (0.73-0.86)<.001
    Patient age (beyond 16 y after HCT), y*
     <150.79 (0.62-1.01).0620.77 (0.60-0.99).04
     15-291.00 (reference)1.00 (reference)
     30-390.89 (0.64-1.24).490.87 (0.62-1.22).43
     ≥400.66 (0.44-0.99).050.66 (0.44-1.00).05
    Patient sex
     Male1.00 (reference)1.00 (reference)
     Female1.11 (1.05-1.18)<.0011.12 (1.06-1.19)<.001
    Disease
     Standard-risk malignancy1.00 (reference)1.00 (reference)
     High-risk malignancy0.84 (0.79-0.90)<.0010.86 (0.81-0.92)<.001
     Nonmalignant disease1.21 (1.12-1.30)<.0011.14 (1.06-1.24).001
    Conditioning
     Myeloablative1.00 (reference)
     Reduced intensity0.97 (0.91-1.04).40
     Unknown intensity1.11 (1.03-1.20).005
    Donor type
     Related BM1.00 (reference)1.00 (reference)
     Related PBSC0.92 (0.84-1.01).0811.05 (0.95-1.16).37
     Unrelated BM1.13 (1.06-1.20)<.0011.19 (1.11-1.27)<.001
     Unrelated PBSC0.52 (0.08-3.47).500.56 (0.09-3.33).53
     Cord blood0.82 (0.64-1.05).110.88 (0.68-1.13).31
     Haploidentical related0.94 (0.85-1.03).190.98 (0.88-1.09).73
    HLA matching
     Match1.00 (reference)
     Mismatch1.00 (0.94-1.07).89
    Year of transplantation
     1974-19990.96 (0.90-1.02).160.92 (0.86-0.99).017
     2000-20051.00 (reference)1.00 (reference)
     2006-20130.86 (0.80-0.93)<.0010.86 (0.80-0.93)<.001
    Maximum grade of acute GVHD
     Grade 0-I1.00 (reference)
     Grade II0.91 (0.85-0.97).005
     Grade III-IV0.84 (0.76-0.93).001
    Chronic GVHD before 2 y
     None1.00 (reference)1.00 (reference)
     Limited0.82 (0.77-0.88)<.0010.82 (0.77-0.89)<.001
     Extensive0.67 (0.63-0.72)<.0010.67 (0.62-0.72)<.001
    • BM, bone marrow; PBSC, mobilized blood cells.

    • * Separate analyses were performed before and after 16 years because of the violation of proportional assumption.

    • Cord blood and haploidentical transplantation were excluded.

  • Table 3.

    The last performance status in patients who terminated follow-up (N = 4987)

    Patient age at transplantation, yECOG performance status at the last follow-up
    0≥1Unknown
    All patients3502 (70)868 (17)617 (12)
    <15676 (58)112 (10)379 (32)
    15-291180 (79)182 (12)123 (8)
    30-39678 (79)152 (18)31 (4)
    ≥40968 (66)422 (29)84 (6)
  • Table 4.

    Details of follow-up termination at 1 representative center (N = 355)

    ECOG performance status at the last follow-upPerson who made the decision, no. (%)
    PhysicianPatient
    All patients
     0241 (83)49 (17)
     ≥113 (39)20 (61)
     Unknown21 (66)11 (34)
    Age <15 y at HCT
     0129 (83)26 (17)
     ≥17 (58)5 (42)
     Unknown12 (63)7 (37)
    Age 15-29 y at HCT
     050 (81)12 (19)
     ≥10 (0)1 (100)
     Unknown3 (60)2 (40)
    Age 30-39 y at HCT
     027 (87)4 (13)
     ≥11 (13)7 (88)
     Unknown3 (75)1 (25)
    Age ≥40 y at HCT
     035 (83)7 (17)
     ≥15 (42)7 (58)
     Unknown3 (75)1 (25)