Page 1453 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 80 Clinical Manifestations, Staging, and Treatment of Follicular Lymphoma 1293

TABLE Chemotherapy Regimens in Indolent Lymphomas
80.8
BR (Every 28 Days) ProMACE-MOPP
2
Bendamustine 120 mg/m days 1 and 2 Cycles repeated every 28 days
2
Rituximab 375 mg/m IV day 1 Day 1
CVP-R (Every 21 Days) Cyclophosphamide 650 mg/m IV
2
2
Cyclophosphamide 750 mg/m IV on day 1 Doxorubicin 25 mg/m IV
2
2
Vincristine1.4 mg/m , up to a maximal dose of 2 mg IV, on day 1 Etoposide 120 mg/m IV
2
2
Prednisone 40 mg/m daily PO days 1–5 Prednisone 60 mg/m orally daily days 1–14
2
Rituximab 375 mg/m IV day 1 32 Day 8
2
R-CHOP (Every 21 Days) Mechlorethamine 6 mg/m IV
2
Cyclophosphamide 750 mg/m IV on day 1 Vincristine 1.4 mg/m (maximum 2 mg) IV on day 8
2
2
Doxorubicin 50 mg/m IV on day 1 Procarbazine 100 mg/m orally daily days 8–14
2
2
Vincristine1.4 mg/m , up to a maximal dose of 2 mg IV, on day 1 Day 15
2
Prednisone 100 mg daily orally on days 1–5 Methotrexate 500 mg/m IV on day 15 with leucovorin 50 mg/m orally
2
2
2
Rituximab 375 mg/m IV on day 1 of each therapy cycle or by alternate every 6 hours for four doses beginning 24 hours after methotrexate
33
schedule 34 R-Hyper-CVAD (Every 21 Days) 36
CNOP (Every 21 Days) Cycles 1, 3, 5 and 7
Cyclophosphamide 750 mg/m IV on day 1 Rituxuimab 375 mg/m IV on day 1
2
2
2
Mitoxantrone 10 mg/m IV on day 1 Cyclophosphamide (with mesna) 300 mg/m IV over 3 hours every 12
2
2
Vincristine1.4 mg/m , up to a maximal dose of 2 mg IV, on day 1 hours on days 2–4 (total 6 doses)
2
Prednisone 50 mg/m daily orally on days 1–5 Vincristine 1.4 mg/m (maximum 2 mg) IV on days 5 and 12
2
R-CHVP-IFN (Every 28 Days for 6 Months, Then Every 2 Months for 6 Doxorubicin 16.6 mg/m IV by continuous infusion on days 5–7
2
Months). 35 Dexamethasone 40 mg/day PO/IV on days 2–5 and days 12–15.
Cyclophosphamide 600 mg/m 2 Cycles 2,4, 6 and 8
Doxorubicin 25 mg/m 2 Rituxuimab 375 mg/m IV on day 1
2
Etoposide 100 mg/m on day 1 (replaces original teniposide 60 mg/m on Methotrexate 200 mg/m IV over 2 hours, followed by 800 mg/m IV
2
2
2
2
day 1) continuous infusion over 22 hours on day 2
2
Prednisolone 40 mg/m on days 1–5 Leucovorin 50 mg PO starting 12 hours after completion of methotrexate
Interferon-α 5–3 times a week infusion, followed by 15 mg PO every 6 hours for 8 dosed until the
Patients being treated with R-CHVP also received 375 mg/m of rituximab methotrexate level is less than 0.1 µM/L.
2
IV on day 1 of each therapy cycle for 6 cycles Cytarabine 3000 mg/m IV over 2 hours every 12 hours on days 3 and 4
2
FMD (Every 28 Days) (4 doses total)
2
Fludarabine 25 mg/m IV on day 1–3 Rituximab Monotherapy
2
Mitoxantrone 10 mg/m IV on day 1 Rituximab 375 mg/m weekly for 4 weeks
2
Dexamethasone 20 mg /day PO days 1–5
2
Patients being treated with R-FMD also received 375 mg/m of rituximab
IV on day 1 of each therapy cycle
28
compared with watchful waiting. A total of 463 patients were Although there are little available data to suggest that we should
2
randomly assigned to watchful waiting, rituximab 375 mg/m weekly change our practice of “watch and wait” for the asymptomatic low-
for 4 weeks (rituximab induction), or rituximab induction followed bulk patients, data suggest that this practice is becoming much less
31
by a maintenance schedule of 12 further infusions given at 2-monthly common in the United States. The National Lymphocare study is
intervals for 2 years (maintenance rituximab). The rituximab induc- a prospective observational study designed to assess presentation,
tion arm was closed early and the study continued to accrue to the prognosis, treatment, and clinical outcomes in newly diagnosed FL.
other two arms. There was a significant difference in the time to start The treating physician determines management according to clinical
of next treatment, with 46% of watchful waiting patients still not judgment with no prescribed treatment regimen and data regarding
needing treatment at 3 years compared with 88% in the maintenance histology, stage, therapy, response, relapse, and death are recorded.
rituximab group (p <.0001) and 78% in the rituximab induction Among 2708 patients enrolled at 265 centers, only 17.7% of patients
group. were initially observed and of these, 22% received active therapy
A major clinical trial question is whether identification of clinical within 1 year and 31% within 2 years, the majority with chemoim-
or molecular risk factors can guide which patients are candidates for munotherapy. This observation is in stark contrast to the data from
early therapy. A survival predictor score has also been developed from the BNLI study which demonstrated, that, when censored for non-
4
gene expression profiling studies. The results from this study suggest lymphoma death, 19% of patients and 40% of those older than 70
that the molecular determinants of biologic heterogeneity are already years who were randomized to expectant management still did not
present in the diagnostic LN biopsies rather than by the later acquisi- require therapy at 10 years. 27
tion of secondary genetic changes. A major component of the gene
expression prognostic signature is related to immune cells in the
tumor microenvironment. 11,12,29 Whereas it is to be hoped that in the TREATMENT APPROACHES
future guidelines for treatment will be based upon clinical staging
systems, genetic profiles, and immune response signatures, it has not Treatment is indicated in patients with symptomatic disease, bulky
yet been established which factors help us to decide who should have lymphadenopathy and/or splenomegaly, risk of local compressive
immediate therapy. This may well have practical implications since disease, marrow compromise, or steady progression of disease. Once
it has been demonstrated that patients who progress within 2 years indicated, numerous treatment approaches are available (Table 80.8).
30
of diagnosis have poorer outcome and might well benefit from The concept that the approach can be to “do nothing” or discuss an
earlier institution of treatment. approach with considerable morbidity and mortality even including