Table 1.
Treatment Details
| Treatment No. | Drugs/Procedures | Doses/Schedules |
|---|---|---|
| 1, 2, 2.5* (R-M-CHOP) | Rituximab† | 375 mg/m2 IV on day 1 |
| Methotrexate | 300 mg/m2 IV over 4 hours on day 2 | |
| Leucovorin | 50 mg/m2 IV every 6 hours for three doses starting 24 hours after completing methotrexate, then 10 mg/m2 IV or PO every 6 hours until serum methotrexate level is < 0.05 μM | |
| Cyclophosphamide | 2,000 mg/m2 IV over 2 hours on day 3 | |
| Doxorubicin | 50 mg/m2 IV on day 3 | |
| Vincristine | 1.4 mg/m2 IV on day 3 (cap the dose at 2 mg if patient is > 40 years old) | |
| Prednisone | 100 mg/m2 PO daily on days 3-7 | |
| G-CSF | 5 μg/kg SQ daily starting on day 4 until neutrophils > 10,000/μL once or > 5,000/μL twice | |
| Levofloxacin | 500 mg PO daily starting on day 6 until neutrophils ≥ 1,500/μL | |
| Fluconazole | 200 mg PO daily starting on day 6 until neutrophils ≥ 1,500/μL | |
| 3 (EAR) | Etoposide | 40 mg/kg IV over 96 hours on days 1-4 |
| Cytarabine | 2,000 mg/m2 IV over 2 hours twice daily on days 1-4 | |
| Rituximab | 375 mg/m2 IV on day 6 and day13 (two total doses) | |
| G-CSF | 10 μg/kg SQ daily starting on day 14 until completion of peripheral blood stem-cell collection | |
| Leukapheresis | Begin daily when WBC is ≥ 5,000/μL | |
| Levofloxacin | 500 mg PO daily starting on day 7 until neutrophils ≥ 500/μL | |
| Fluconazole | 200 mg PO daily starting on day 6 until neutrophils ≥ 500/μL | |
| Acyclovir | 200 mg PO three times daily starting on day 6 to continue until 1 year post-ASCT | |
| 4 (CBV) | Carmustine | 15 mg/kg (maximum, 550 mg/m2) IV over 1 hour on day –6 |
| Etoposide | 60 mg/kg IV over 4 hours on day –4 | |
| Cyclophosphamide | 100 mg/kg IV over 2 hours on day −2 | |
| Infusion of peripheral-blood stem cells | Day 0 | |
| G-CSF | 5 μg/kg SQ daily starting on day +4 until neutrophils > 5,000/μL once or > 1,500/μL twice | |
| Levofloxacin | 500 mg PO daily starting on day +2 until neutrophils ≥ 500/μL | |
| Fluconazole | 200 mg PO daily starting on day +1 until neutrophils ≥ 500/μL | |
| Acyclovir | 200 mg PO three times daily starting on day −2 to continue until 1 year post-ASCT | |
| Trimethoprim/sulfamethoxazole | One double-strength tablet PO twice every Saturday and Sunday to continue until 3 months post-ASCT | |
| 5 (post-ASCT immunotherapy) | Rituximab | 375 mg/m2 IV weekly for two doses in weeks 6 and 7 after ASCT |
NOTE. All chemotherapy doses were based on a corrected body weight (in kilograms) defined as ideal weight +0.25 (actual weight − ideal weight).23 When the actual weight was less than the ideal weight, the corrected weight was the actual weight. For patients of more than 150% of ideal weight, the corrected weight was capped at 112.5% of ideal weight. The median days between start of Treatments were as follows: between Treatments 1 and 2, median = 23 days (range, 16-41 days); between Treatments 2/2.5 and 3, median = 30 days (range, 14-52 days); between Treatments 3 and 4, median = 54 days (range, 38-92 days); and between Treatments 4 and 5, median = 42 days (range, 13-327 days).
Abbreviations: R-M-CHOP, rituximab, methotrexate, cyclophosphamide (augmented dose), doxorubicin, vincristine, and prednisone; IV, intravenous; PO, per os (by mouth); G-CSF, granulocyte-colony stimulating factor (filgrastim); SQ, subcutaneously; EAR, high-dose etoposide and cytarabine with rituximab; ASCT, autologous stem-cell transplantation; CBV, high-dose carmustine, etoposide, and cyclophosphamide.
Treatment 2.5 is given if the pre-Treatment 3 bone marrow biopsy contains > 15% MCL. Ten patients needed Treatment 2.5.
Rituximab is withheld if circulating mantle cells are > 10,000/μL.