Calc Function

    • Calcs that help predict probability of a diseaseDiagnosis
    • Subcategory of 'Diagnosis' designed to be very sensitiveRule Out
    • Disease is diagnosed: prognosticate to guide treatmentPrognosis
    • Numerical inputs and outputsFormula
    • Med treatment and moreTreatment
    • Suggested protocolsAlgorithm

    Disease

    Select...

    Specialty

    Select...

    Chief Complaint

    Select...

    Organ System

    Select...

    Patent Pending

    Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI)

    Predicts survival after HCT in patients with hematologic malignancies, including optional age adjustment.
    Favorite

    INSTRUCTIONS

    Entering age to obtain age-adjusted HCT-CI is optional. The original HCT-CI (without age adjustment) is still considered the standard.

    When to Use
    Pearls/Pitfalls
    Why Use

    Patients with hematologic malignancies for whom allogeneic hematopoietic cell transplantation (allo-HCT) or autologous stem cell transplantation (ASCT) is being considered.

    • The HCT-CI predicts non-relapse mortality (NRM) after HCT, based on pre-HCT comorbidities and organ dysfunction.
    • Originally developed as a prognostic comorbidity model for HCT outcomes. A large, prospective, multi-center study (Sorror et al, BBMT 2015) validated its use in predicting NRM and overall survival in patients undergoing allo-HCT and ASCT for hematologic malignancies.
    • A modified HCT-CI incorporating age as a risk factor (aaHCT-CI) was recently studied and validated retrospectively, though the large prospective validation (Sorror et al, J Clin Oncol 2014) was done using the original HCT-CI Score (not the aaHCT-CI).
    • From Sorror 2013, “How I assess comorbidities before hematopoietic cell transplantation”:
      • By itself, the score is not intended to recommend which patients should or should not be treated with allogeneic HCT. Ultimately, this decision comes down to the treating physician and the patient.
      • When patients are assessed with pulmonary function testing, only pre-bronchodilator values of FEV₁ are used for the HCT-CI, and DLco should be corrected for hemoglobin using the Dinakara equation.
    • May help clinicians decide the appropriateness of proceeding with HCT, or to choose the appropriate conditioning regimen intensity for individual patients undergoing HCT.
    • Can also be used in statistical analyses to compare the baseline risk of NRM among different patients and studies.
    • Has become a routinely reported tool in many subsequent studies within the field of HCT, particularly if the study assesses the incidence of NRM.
    None
    0
    Afib/flutter, SSS, or ventricular arrhythmias
    +1
    None
    0
    CAD, CHF, MI, or EF ≤50%
    +1
    Valvular disease (except mitral prolapse)
    +3
    None
    0
    Crohn disease or ulcerative colitis
    +1
    None or diet-controlled
    0
    Treated w/insulin or oral hypoglycemics
    +1
    None
    0
    CVA or TIA
    +1
    None
    0
    Depression or anxiety requiring psych consult or treatment
    +1
    None
    0
    Chronic hepatitis (bilirubin >ULN to 1.5× ULN, or AST/ALT >ULN to 2.5× ULN)
    +1
    Liver cirrhosis (bilirubin >1.5× ULN, or AST/ALT 2.5× ULN)
    +3
    No
    0
    Yes
    +1
    None or abx only on day 0
    0
    Requiring continuation of abx after day 0
    +1
    None
    0
    SLE, RA, polymyositis, mixed CTD, or polymyalgia rheumatica
    +2
    None or not requiring treatment
    0
    Requiring treatment
    +1
    None or serum Cr ≤2 mg/dL (177 µmol/L), not on dialysis, and no prior renal transplant
    0
    Serum Cr >2 mg/dL (177 µmol/L), on dialysis, or prior renal transplant
    +2
    None or mild
    0
    DLco and/or FEV₁ 66%–80%, or dyspnea on slight activity
    +2
    DLco and/or FEV1 ≤65% or dyspnea at rest or requiring oxygen
    +3
    None or nonmelanoma skin cancer
    0
    Treated at any point in the patient’s history
    +3
    Allo-HCT
    ASCT

    Result:

    Please fill out required fields.

    Next Steps
    Evidence
    Creator Insights

    Advice

    Should be used in shared decision making with the physician and patient regarding treatment options, not to dictate who should and should not undergo HCT.

    Formula

    Addition of the selected points:

     

    0 points

    1 point

    2 points

    3 points

    History of arrhythmia

    None

    Atrial fibrillation or flutter, sick sinus syndrome, or ventricular arrhythmias

    --

    --

    Cardiac dysfunction

    None

    CAD*, CHF, MI, or EF ≤50%

    --

    Heart valve disease (except mitral valve prolapse)

    Inflammatory bowel disease

    None

    Crohn disease or ulcerative colitis

    --

    --

    Diabetes

    None or diet-controlled

    Treated with insulin or oral hypoglycemics

    --

    --

    Cerebrovascular disease

    None

    CVA or TIA

    --

    --

    Psychiatric disturbance

    None

    Depression or anxiety requiring psychiatric consult or treatment

    --

    --

    Hepatic dysfunction

    None

    Chronic hepatitis (bilirubin >ULN to 1.5× ULN, or AST/ALT >ULN to

    2.5× ULN)

    --

    Liver cirrhosis (bilirubin >1.5× ULN, or AST/ALT  2.5× ULN)

    Obesity (BMI ≥35 kg/m2)

    No

    Yes

    --

    --

    Infection

    None or antibiotics only on day 0

    Requiring continuation of antimicrobial treatment after day 0

    --

     --

    Rheumatologic disease

    None

    --

    SLE, RA, polymyositis, mixed CTD, or polymyalgia rheumatica

     --

    Peptic ulcer

    None or not requiring treatment

    Requiring treatment

    --

    --

    Renal dysfunction

    None or serum creatinine ≤2 mg/dL (177 µmol/L), not on dialysis, and no prior renal transplant

    --

    Serum creatinine >2 mg/dL (177 µmol/L), on dialysis, or prior renal transplant

     --

    Pulmonary dysfunction

    None or mild

    --

    DLco** and/or FEV₁ 66%–80%, or dyspnea on slight activity

    DLco and/or FEV1 ≤65% or dyspnea at rest or requiring oxygen

    Prior solid tumor

    None or nonmelanoma skin cancer

     --

     --

    Treated at any point in the patient’s history

    For age-adjusted HCT-CI (aaHCT-CI, optional):

    Age (years)

    <40

    ≥40

    --

    -- 


    *One or more vessel-coronary artery stenosis requiring medical treatment, stent, or bypass graft.

    **Dinakara equation for DLco:

    DLco (% predicted normal) = 6.07 + 6.49 × Hgb (in mg/dL)

    Facts & Figures

    Interpretation:

    Allo-HCT (All types of patients and transplants: nonmyeloablative, reduced-intensity conditioning, myeloablative conditioning):

     

    HCT-CI Score

    0

    1–2

    ≥3

    1-year

    NRM

    17%

    21%

    26%

    OS

    69%

    62%

    56%

    3-year

    NRM

    24%

    28%

    35%

    OS

    54%

    47%

    38%


    ASCT
    (All types of patients and transplants):

     

    HCT-CI Score

    0

    1–2

    ≥3

    1-year

    NRM

    3%

    3%

    5%

    OS

    91%

    88%

    86%

    3-year

    NRM

    5%

    6%

    9%

    OS

    79%

    73%

    70%

    Age-adjusted HCT-CI (Allo-HCT only, including patients undergoing allo-HCT for nonmalignant diseases):

     

    aaHCT-CI Score

    Allo-HCT only

    0

    1–2

    3–4

    ≥5

    2-year

    NRM

    NMA: 5%

    RIC: 12%

    MAC: 10%

    NMA: 9%

    RIC: 18%

    MAC: 20%

    NMA: 17%

    RIC: 36%

    MAC: 37%

    NMA: 35%

    RIC: 41%

    MAC: 49%

    OS

    NMA: 81%

    RIC: 87%

    MAC: 79%

    NMA: 74%

    RIC: 70%

    MAC: 66%

    NMA: 59%

    RIC: 50%

    MAC: 45%

    NMA: 37%

    RIC: 35%

    MAC: 29%

    NRM, non-relapse mortality. OS, overall survival. NMA, nonmyeloablative. RIC, reduced-intensity conditioning. MAC, myeloablative conditioning.

    Evidence Appraisal

    The HCT-CI was developed by Sorror et al from the Charlson Comorbidity Index. It incorporates several additional comorbidities and several specific measures of organ function, each of which is converted into weighted points, which are summed into a score that is predictive of NRM. The HCT-CI was developed at Fred Hutchinson Cancer Research Center (FHCRC) then initially validated in large cohorts of patients undergoing allogeneic HCT at FHCRC and MD Anderson Cancer Center, and in other single institution patient cohorts in the context of both myeloablative and reduced-intensity conditioned HCT.

    The HCT-CI is now routinely captured data by all transplant centers and submitted to the Center for International Blood and Marrow Transplantation Research (CIBTMR) to compare outcomes.

    Since its inception, the score has also been extended in use to patients undergoing high-dose therapy and autologous stem cell transplantation (HDT-ASCT). Of note, however, given that NRM after HDT-ASCT is generally much less common, the HCT-CI is generally not used as often as it is in the allogeneic HCT setting.

    More recently, Sorror et al added age into the calculation of the score, improving its predictive value and allowing for better incorporation of the prognostic role of age in transplantation decision-making. It is important to note that this was studied only in patients undergoing allo-HCT and included a group of patients undergoing allo-HCT for non-malignant diseases.

    Multiple investigators at several centers confirmed the significance of the HCT-CI, though several did not. Given this, a large prospective multi-center observational study (8,115 allo-HCT patients and 11,652 ASCT patients) was undertaken via the CIBMTR to definitively validate the predictive power of the HCT-CI for patients undergoing their first autologous and allogeneic hematopoietic cell transplantations for hematologic malignancies. The main outcomes of interest were NRM and OS. This study confirmed the validity of the HCT-CI in both allo-HCT and ASCT (Sorror et al, BBMT 2015). Main results:

    • In both allo-HCT and ASCT, and in all sub-groups even when adjusting for diagnosis, age and conditioning intensity, an HCT-CI  ≥3 was associated with higher NRM and lower overall survival.
    • Allo-HCT patients <18 years old or those receiving reduced-intensity condition (RIC) or nonmyeloablative (NMA) regimens with scores 1 and 2 had similar NRM and OS when compared to those with score 0.
    • For ASCT, patients with scores 1 and 2 had similar NRM, but lower OS when compared to patients with score 0, and non-significant higher risk of NRM, but significantly higher risk of overall mortality compared with those with score 0. Patients with scores ≥3 had significantly higher NRM and higher risk of overall mortality.

    Allogeneic Hematopoietic-cell Transplantation (Allo-HCT), all patients, all types of patients and transplants (NMA, RIC, and MAC)

     

    HCT-CI Score

    0

    1–2

    ≥3

    1 year

    NRM

    17%

    21%

    26%

    OS

    69%

    62%

    56%

    3 years

    NRM

    24%

    28%

    35%

    OS

    54%

    47%

    38%


    In sub-group analyses:

    • Adjusting for high-dose conditioning (MAC vs. RIC/NMA):
      • Patients receiving MAC with HCT-CI of 1–2 and ≥3 had higher risk of NRM and OS compared with those with score 0, and had higher probabilities of NRM and lower OS in general.
      • However, patients receiving RIC/NMA with scores 1–2 had similar NRM and OS, but those with score ≥3 had higher NRM and lower OS when compared to those with score 0.
    • When comparing children vs. adults:
      • Adults with scores 1–2 and ≥3 had higher NRM and lower OS when compared to score 0.
      • For children, scores ≥3 were associated with higher risk of NRM and lower OS when compared to score 0, but not when compared to scores 1–2.

    Autologous Stem Cell Transplantation (ASCT), all types of patients and transplants

     

    HCT-CI Score

    0

    1–2

    ≥3

    1 year

    NRM

    3%

    3%

    5%

    OS

    91%

    88%

    86%

    3 years

    NRM

    5%

    6%

    9%

    OS

    79%

    73%

    70%


    For ASCT, patients with scores 1–2 had non-significant higher risk of NRM, but significantly higher risk of overall mortality compared with those with score 0. Patients with scores ≥3 had significantly higher NRM and higher risk of overall mortality.

    In sub-group analysis:

    • When comparing patients getting ASCT for multiple myeloma vs. lymphoma (the two most significant indications for ASCT), for both groups, patients with scores 1–2 had non-significant higher risk of NRM, but significantly higher risk of overall mortality compared with those with score 0. Patients with scores ≥3 had significantly higher NRM and higher risk of overall mortality.

    Literature

    Validation

    Research PaperSorror ML, Giralt S, Sandmaier BM, et al. Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood. 2007;110(13):4606-13.Research PaperSorror ML, Logan BR, Zhu X, et al. Prospective Validation of the Predictive Power of the Hematopoietic Cell Transplantation Comorbidity Index: A Center for International Blood and Marrow Transplant Research Study. Biol Blood Marrow Transplant. 2015;21(8):1479-87.Research PaperMaruyama D, Fukuda T, Kato R, et al. Comparable antileukemia/lymphoma effects in nonremission patients undergoing allogeneic hematopoietic cell transplantation with a conventional cytoreductive or reduced-intensity regimen. Biol Blood Marrow Transplant 2007;13(8):932-941.Research PaperLim ZY, Ingram W, Brand R, et al. Impact of pretransplant comorbidities on alemtuzumab-based reduced-intensity conditioning allogeneic hematopoietic SCT for patients with high-risk myelodysplastic syndrome and AML. Bone Marrow Transplant. 2010;45(4):633-9.Research PaperSorror ML, Sandmaier BM, Storer BE, et al. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol. 2007;25(27):4246-54.Research PaperSorror ML, Sandmaier BM, Storer BE, et al. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. JAMA. 2011;306(17):1874-83.Research PaperSaad A, Mahindra A, Zhang MJ, et al. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2014;20(3):402-408.e1.
    Dr. Mohamed Sorror

    About the Creator

    Mohamed Sorror, MD, is an associate professor of medicine at the University of Washington. He is also an associate member of the clinical research division at Fred Hutchinson Cancer Research Center. Dr. Sorror’s research interests are focused on hematological malignancies.

    To view Dr. Mohamed Sorror's publications, visit PubMed

    Content Contributors
    • Michael Scordo, MD
    About the Creator
    Dr. Mohamed Sorror
    Content Contributors
    • Michael Scordo, MD