The Burkitt Lymphoma International Prognostic Index
Prof Adam Olszewski - Brown University, Providence, USA
At this ASH meeting we are presenting an international collaboration that developed the Burkitt Lymphoma International Prognostic Index, abbreviated to BLIPI by common decision. The motivation for this study was that Burkitt lymphoma is clinically typically treated quite homogenously, although clinicians are used to sub-stratifying the disease according to historical definitions of low risk, which is actually very rare and usually indicates a single or very localised disease, so that is resectable, and with a normal LDH, and high risk disease, which we encounter with our other patients which are not further sub-stratified in any consistent manner.
The traditional international prognostic index developed in the ‘80s and ‘90s for aggressive lymphomas is not very useful because most cases of the Burkitt’s lymphoma have advanced stage, stage 3 or 4, and have abnormal LDH, so two of the traditional IPI factors and covers the vast majority of patients.
To develop a Burkitt Lymphoma specific index we have used a collaboration between thirty cancer centres in the United States who submitted their retrospective data on patients treated for Burkitt’s lymphoma over the past decade. We developed this index using 633 cases of patients who received active therapy. We established that the foremost prognostic factors in Burkitt’s lymphoma for progression free survival were age equal to 40 or over, LDH higher than three times the upper normal limit, so unlike in the IPI where there was non-upper limit of normal here it’s three times the upper limit of normal, as well as poor performance status, ECOG 2, 3 o4 4, and involvement of the CNS which was observed in 19% of patients in this cohort.
These four factors can stratify Burkitt’s lymphoma into a low risk group, when there is no risk factor present, intermediate group with one risk factor and high risk group when at least two of these factors are present.
The low risk group is larger than the traditionally defined low risk group; it encompasses approximately 18% of patients. Some of them have increased LDH and some of them have advanced disease and yet their prognosis is excellent, just like for the patients who have more localised disease. So the progression free survival at three years for patients who have low-risk Burkitt lymphoma exceeds 90% while the high risk group, which encompasses half of patients, has a progression free survival of somewhere between 50-60%, in our cohort it was 53%. But we also validated these findings in an external cohort of patients that was about 457 patients treated in Europe, Canada and Australia. In this cohort the calibration of this index showed that the outcomes were somewhat higher in each category so even the poor risk category had progression free survival at three years of slightly over 60%.
Still this index allows us to stratify patients into this larger low-risk group for whom we know that the prognosis will be excellent. Potential future research could target this group for a somewhat de-escalated therapy, just like recently has been shown with the dose-adjusted EPOCH regimen where patients with truly very localised disease received only three cycles of chemotherapy without any intrathecal prophylaxis and had excellent outcomes.
On the other hand, the high risk group, which is still about half of patients with Burkitt’s lymphoma, truly have inadequate outcomes with current treatment and they can also be targeted in future trials for augmented or novel approaches using some of the targeted agents that we have.
Altogether, this index is derived from retrospective data so it currently should not be used for any treatment modification but can be used to compare risk distribution across different trials - Burkitt’s lymphoma trials are often single arm, they are difficult to compare otherwise – and can also be used for the design of future clinical trials defining these groups.
It is quite interesting that both the clinical characteristics and outcomes and the risk distribution of patients with Burkitt lymphoma was very, very similar between the North American cohorts and the European, Canadian, Australian cohorts with some differences in the CNS involvement and performance status. We hope that this Burkitt Lymphoma International Prognostic Index will be used by clinicians and researchers to help design better treatments for this disease.