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Hoelzer Regimen (BFM)

Abstract: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults.

In a prospective multicenter study, 368 acute lymphoblastic leukemia (ALL) patients aged 15 to 65 years were treated with an intensified induction and reinduction regimen; 272 (73.9%) achieved complete remission (CR). The median remission duration (MRD) is 24.3 months, and the probability of being in continuous CR (CCR) at greater than 5 years is .37. The median survival for all 368 patients is 27.5 months, and the probability of being alive at 5 years is .39. For the 272 patients in remission the median survival is 58.4 months, and the probability of being alive at 5 years is .49. A lower CR rate was seen for patients with bleeding at diagnosis or with splenomegaly/hepatosplenomegaly. The prognostic factors unfavorable for remission duration were time to CR greater than 4 weeks v less than 4 weeks (P = .0002), age greater than 35 years v less than 35 years (P = .0008), leukocyte count greater than 30,000/microL v less than 30,000/microL (P = .0112), and null ALL v common ALL (c-ALL)/T cell ALL (T-ALL) (P = .05). The remission duration correlated strongly (P = .0001) with the number of these independent prognostic factors. In patients with none of these adverse factors the MRD has not yet been reached, with one adverse factor the MRD is 21.9 months, and with two or three adverse factors the MRD is only 9.6 months. For the immunologic subtype T-ALL, the probability of being in CCR at greater than 5 years is .55; for c-ALL, .34; and for null ALL, .24. According to these results, patients were stratified into a low-risk group with a CCR rate of .62 and a high-risk group with a CCR rate of .28, with the latter now allocated to either further chemotherapy or bone marrow transplantation in first remission.

References

Hoelzer D, Thiel E, Loffler H, Buchner T, Ganser A, Heil G, Koch P, Freund M, Diedrich H, Ruhl H, et al. Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 1988; 71:123 - 131

Regimen

Induction - Phase I

  • Vincristine 2 mg IV days 1,8,15,22
  • Daunorubicin 25 mg / M2 IV days 1,8,15,22
  • Prednisone 60 mg / M2 PO days 1 - 28
  • L - asparaginase 5,000 units / M2 IV days 1 - 14

Induction - Phase II

  • Cyclophosphamide 650 mg / M2 IV days 29,43,57 maximum dose 1000 mg
  • Ara - C 75 mg / M2 IV days 31 - 34,38 - 41, 45 - 48, 52 - 55
  • 6 - Mercaptopurine 60 mg / M2 PO days 29 - 57

CNS Prophylaxis -- weeks 5 - 8

  • Methotrexate 10 mg / M2 IT days 31,38,45,52 maximum dose is 15 mg
  • Cranial radiotherapy 1800 - 2400 cGy given with phase II induction radiotherapy

Consolidation - Phase I -- begins week 20

  • Vincristine 2 mg IV days 1,8,15,22
  • Doxorubicin 25 mg / M2 IV days 1,8,15,22
  • Dexamethasone 10 mg / M2 PO days 1 - 28

Consolidation -- Phase II

  • Cyclophosphamide 650 mg / M2 IV day 29 maximum dose is 1000 mg
  • Ara - C 75 mg / M2 IV days 31 - 34,38 - 41
  • 6 - Thioguanine 60 mg / M2 PO days 29 - 42

Maintenance

  • 6 - Mercaptopurine 60 mg / M2 PO  daily weeks 10 - 18,29 - 130
  • Methotrexate 20 mg / M2 PO / IV weekly weeks 10 - 18,29 - 130

     
  Summary  
  Complete Response Rate 73.9%
  Median Remission Duration 24.3 months
  Median Survival 27.5 months
  Toxicity  
     

Article reviewed by:

Dr. Tamer Fouad, M.D.

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