International Prognostic Index (IPI) Predicts Outcome after Histological Transformation of Low Grade Non-Hodgkin Lymphoma.
Ivana N. M. Micallef, Ellen D. Remstein, Stephen M. Ansell, Jason T. Lewis, Kay Ristow, Thomas M. Habermann. Division of Hematology, Mayo Clinic, Rochester, MN, USA; Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA
Histological transformation of low grade Non-Hodgkin lymphoma to intermediate grade disease is well recognized and overall is associated with a poor prognosis.
To determine factors, which affect overall survival in patients with transformed disease, patients were identified who had at least a six month interval from date of diagnosis of low grade disease until time of transformation, and their medical records were reviewed.
Patients with follicular lymphoma (grade 3) at original diagnosis or transformation were excluded.
From November 1979 to January 2000, 58 patients (33 female: 25 male) who met the inclusion criteria were identified. At the time of original diagnosis of low grade lymphoma, median age was 56 years (range 32-82 years).
The diagnoses was follicular lymphoma in 43 patients (grade 1: 33; grade 2:10);
- marginal zone lymphoma or MALT lymphoma in 9;
- small lymphocytic lymphoma or chronic lymphocytic leukemia in 4;
- lymphoplasmacytic lymphoma in 1,
- and a single patient had composite follicular lymphoma and small lymphocytic lymphoma.
Forty-three patients had advanced stage disease (stage III or IV).
International prognostic index (IPI) at the diagnosis of low grade lymphoma was
- 0-1 in 34 patients,
- 2-3 in 22 patients
- and not available in 2.
The median number of treatment regimens prior to transformation was 2 (range 0-9).
The time from original diagnosis to transformation was a median of 4.2 years (range 8 months-20 years).
Characteristics at time of transformation included:
- a median age of 64 years (range 34-86),
- a diagnoses of diffuse large cell lymphoma in all cases,
- advanced stage disease in 54 patients,
- B symptoms in 9,
- elevated LDH in 17,
- and extra-nodal disease in 38.
IPI at time of transformation was
- 0-1 in 16 patients,
- 2-3 in 36 patients
- and 4-5 in 6 patients.
At a median follow up of 14 months from histological transformation (range 3 days-20 years),
- 13 of 58 patients (22%) remained alive
- 6 without evidence of disease
On univariate analysis, the following factors were associated with an improved survival:
at diagnosis -
- age 60 years (p=0.01),
- advanced stage disease (p=0.02),
- positive bone marrow (p=0.02),
- presence of extranodal disease (p=0.05)
and at transformation -
- age 60 (p=0.02),
- performance status 0 -1 (p=0.003),
- lack of B symptoms (p=0.007),
- low or intermediate IPI (p=0.0009)
- and autologous stem cell transplant (SCT, p=0.0009).
On multivariate analysis, factors which remained significant included:
- - age 60 years (p=0.003)
and extranodal disease (p=0.02);
- - lack of B symptoms (p=0.001),
- autologous SCT (p= 0.003),
- and low or intermediate IPI (p=0.0009).
IPI at transformation correlated with overall survival;
- for the low risk group (IPI 0-1)
the median survival was 24 months (range 1-234),
- for the intermediate risk group (IPI 2-3)
the median survival was 13 months (range 2-81),
- and for the high risk group (IPI 4-5)
the median survival was 0.5 months (range 0-25).
In conclusion, histological transformation of low grade non-Hodgkin lymphoma is associated with a poor survival (median survival 14 months from transformation).
The IPI at the time of histological transformation is the most important predictor of overall survival.