HyperCVADHDMTX-AraC

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HyperCVAD/HDMTX-AraC

Dose-intensive phase

Consists of eight cycles of dose-intensive therapy courses of Hyper-CVAD therapy alternating with high-dose MTX and ~AraC (HDMTX/~AraC) therapy

Hyper-CVAD

  • Cyclophosphamide 300 mg/m2 intravenously (IV) over 3 hours every 12 hours for six doses on days 1 through 3

Mesna at the same total dose as cyclophosphamide but given by continuous infusion starting with cyclophosphamide and ending 6 hours after the last dose

  • Vincristine 2 mg IV days 4 and 11
  • Doxorubicin 50 mg/m2 IV day 4
*Dexamethasone 40 mg daily on days 1 through 4 and 11 through 14

HD MTX/~AraC

MTX 200 mg/m2 IV over 2 hours followed by 800 mg/m2 IV over 24 hours on day 1

Folinic acid rescue starting 24 hours after completion of MTX infusion at 15 mg every 6 hours x 8, and increased to 50 mg every 6 hours if MTX levels were more than 20 µmol/L at the end of the infusion, more than 1 µmol/L 24 hours later, or more than 0.1 µmol/L 48 hours after the end of MTX infusion, until levels were lower than 0.1 µM

 Ara-C 3 g/m2 over 2 hours every 12 hours x 4 on days 2 and 3
 Methylprednisolone 50 mg IV twice daily on days 1 through 3. 

CNS prophylaxis

 MTX 12 mg IT on day 2 and ara-C 100 mg IT on day 8 of each cycle
 Risk factors: (1) LDH > 600 U/L. (2) proliferative index (% S+G2M) > 14%
 High risk: presence of either one risk factor, or B-cell ALL
 Low risk: no risk factor
 Unknown risk: information not available
 16 IT treatments in high-risk patients
 4 IT treatments in low-risk patients (first 2 cycles)
 8 IT treatments in unknown-risk patients (first 4 cycles)

Prophylaxis was given during the dose-intensive (induction-consolidation) phase

 ciprofloxacin 500 mg orally twice daily or levofloxacin 500 mg daily
 fluconazole 200 mg orally daily
 acyclovir 200 mg orally twice daily or valacyclovir 500 mg orally daily

Supportive care with G-CSF

G-CSF 10 µg/kg daily was given in two divided doses starting 24 hours after the end of chemotherapy (ie, on day 5 of Hyper-CVAD therapy and day 4 of HD MTX–ara-C therapy).

Course timing

Subsequent courses of chemotherapy were given as soon as the WBC count was more than 3 x 109/L and the platelet count was more than 60 x 109/L. G-CSF therapy was not interrupted if platelet recovery was delayed, unless the WBC count was greater than 30 x 109/L.

Maintenance phase

Mature B-cell ALL received no maintenance therapy

Ph-positive ALL who were candidates for allogeneic SCT and had a matched related (or one antigen mismatch) donor, or who had a matched unrelated donor, underwent allogeneic SCT as soon as possible in CR (without continuing the intensive phase). Otherwise, maintenance consisted of interferon alfa 5 MU/m2 subcutaneously daily and ara-C 10 mg subcutaneously daily for 2 years.

All other patients received maintenance therapy with mercaptopurine (6-MP), MTX, vincristine, and prednisone (POMP) for 2 years

IV POMP

 6-MP 1 g/m2 IV over 1 hour daily x 5 every month
 MTX 10 mg/m2 IV over 1 hour daily x 5 every month
 Vincristine 2 mg IV monthly
 Prednisone 200 mg daily x 5 monthly with vincristine

It may be reasonable to include oral POMP as no difference was found between the IV and oral regimes:

 6-MP 50 mg tds PO
 MTX 20 mg/m2 weekly PO
 Vincristine 2 mg monthly IV
 Prednisolone 200 mg/day, 5 times per month, with vincristine, PO


Antibiotic prophylaxis given during the maintenance phase

Trimethoprim-sulfamethoxazole twice daily on weekends

Acyclovir 200 mg or valacyclovir 500 mg daily or three times weekly, for the first 6 months.

References

Hagop M. Kantarjian et al, Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia Journal of Clinical Oncology, Vol 18, Issue 3 (February), 2000: 547