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