Haematotox calculator

Version 2

Introduction On this homepage we provide a web-based tool to calculate prognostic scores on haematopoietic toxicity for 6 cycles CHOP-like regimen in patients with aggressive NHL. As we used for this analysis the data collected within the NHL-B1 and NHL-B2 trials of the DSHNHL as described in detail in Pfreundschuh et al. the predictions are valid for similar patient populations.

Description We offer two types of models. Pre-treatment models include beside the therapy regimen only prognostic factors available before treatment start. The prediction concerns all 6 subsequent cycles. In a second class of models we combine pre-treatment factors with the haematotoxicity observed during the first cycle. Hence the prediction is valid for cycles 2 to 6. The models can be applied for leukocytopenia, thrombocytopenia and anaemia. To model prognostic factors for changes in the WHO grades we used the proportional odds model implying that cycle effects are not modelled individually for each patient but in relation to all other cycles. The result of the prediction is a patient allocation to a toxicity risk group and a distribution of WHO grades for haematotoxicity for this group. The prediction will be presented for early cycles (until cycle 3) and later cycles (4-6). The models can support the decision-making process for special care and prophylaxis, but the decision itself has to be made by the physician in charge.

Inclusion criteria before treatment The model has been derived and validated for patients:

• with aggressive NHL aged between 18 and 60 years with an LDH below the upper normal value and patients between 61 and 75 years of age irrespective of the LDH values
• with ECOG performance status 0-3
• with leukocyte counts above 3000/ mm³, thrombocytes above 100.000/ mm³
• without other organ dysfunction
• without bone marrow involvement over 25%
• without other pre-treatment, except a pre-phase treatment with vincristine 2mg and steroids 100mg day 1-7.

Chemotherapy regimen Six cycles of CHOP-21 (3-weekly), CHOP-14 (2 weekly), CHOEP-21 (3 weekly with etoposide 100mg/ m² d1-3) and CHOEP-14 (2 weekly). In the 2 weekly treatments G-CSF is given from day 4 for about 10 days (300 µg/d if <75 kg; 480 µg/d if >=75 kg).

CHO(E)P-schedule

Schemes with the monoclonal anti-CD20 antibody rituximab A validation of our models by an independent data set from the RICOVER60 trial confirmed that our models are also applicable for rituximab containing CHOP-regimens.

Prediction of WHO-grades for haematotoxicity The WHO grades predicted are the following

Missing values for the prognostic factors If there are missing values for the prognostic factors we calculate a worst case scenario and a best case scenario. If there are many missing values the best case and worst case prediction will differ very strong and the models are not meaningful.

Conservative and anticonservative estimations It is possible that the user would like a prediction for a factor combination which includes more factors than the worst chemotherapy cycle observed within the data set of the NHL-B1/B2 trial using for the model building process or less factors than the best cycle of the NHL-B1/B2 trials. Since an extrapolation is not possible, we show the nearest possible prediction and the following hints are printed: ‘a’ for anticonservative predictions, that means the expected toxicity may be lower than the predicted WHO grades express and ‘c’ for conservative predictions, that means the expected toxicity may be higher than the predicted WHO grades express.