AcuteMyeloidLeukemia(AML)                                                                                                       15

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2.   Acute Myeloid Leukemia (AML)

2.4               Pediatric patients

 

2.4.1        General considerations

Over the past decades the cure rate in childhood AML has improved with intensification and optimized timing of induction and postremission therapy.

 

In large randomized trials of postremission therapy superior results have been found for allogeneic bone marrow transplantation over chemotherapy. Data are still insufficient to determine whether autologous bone marrow transplantation is also superior to nonmyeloablative chemotherapy. Low-dose maintenance may be of no benefit after intensive induction and consolidation.

 

Literature: for review and representative group studies e.g.

            AQUINO, Curr. Probl. Pediatr. Adolesc. Health Care 32 (2002): 50-58    

            (review)

            BEHAR et al, Med pediatr. Oncol. 26 (1996): 173-179 (study EORTC-

            58872)

            BLEAKLEy et al, Bone Marrow Transplant 29 (2002): 843-852 (review  

            and  meta-analysis of bone marrow transplantation for pediatric AML)

            GREGORY and ARCECI, Cancer Invest 20 (2002): 1027-1037 ( review

            of risk factors and recent trials)

            O’BRIEN et al, Blood 100 (2002): 2708-2716 (report of consecutive  

            studies of the Australian and New Zealand Children’s Cancer Study Group

            which shows equiefficacy of daunorubicin and idarubicin for remission

            induction, but reduced toxicity for the former)

            PEREL et al, J. Clin. Oncol. 20 (2002): 2774-2782 (study LAME 89/91)

            RAVINDRANATH et al, N. Engl. J. Med. 334 (1996): 1428-1434 (study

            PCG-8821)

            RITTER, Eur. J. Cancer 34 (1998): 862-872

            STEVENS et al, Br. J. Haematol. 101 (1998): 130-140 (study MRC – 10)

 

 

 

Acute Myeloid Leukemia (AML)                                                                                                        23

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            In the following two representative examples of large multi-institutional studies   

            are outlined.

 

2.4.2        Childrens Cancer Group Study 2891

Induction treatment CDCTER

Dexamethasone                      6 mg/m²                 t.i.d. i.v.                             d 1 – 4

Cytarabine                              200 mg/m²             i.v. (cont inf)                     d 1 – 4

Thioguanine                           500 mg/m²             b.i.d. i.v.                            d 1 – 4

Etoposide                              100 mg/m²              i.v. (cont inf)                     d 1 – 4

Cytarabine                       (age-based doses)         i.th.

To be repeated with G-CSF support on days 10 – 14 regardless of response (in patients with Down syndrome on days 14 – 18 or later depending on response).

 

Consolidation treatment

Two additional courses of CDCTER as above.

 

Postinduction treatment

Allogeneic bone marrow transplantation: if a donor is available.

Conventional chemotherapy:  if no donor is available.

 

Course 1

Cytarabine                  3000 mg/m²                b.i.d. i.v. (3 h inf)               d 0-2, 7-9

L-asparaginase           6000 IU/ m²                i.m.                                     h 42

 

Course 2,3

Thioguanine                75 mg/m²                       p.o.                                     d 0 – 27

Vincristine                   1.5 mg/m²                      i.v.                                      d 0

Cytarabine                   75 mg/m²                       i.v.                                      d 0 – 3

Cyclophosphamide      75 mg/m²                      i.v.                                      d 0 –3

Azacytidine                 100 mg/m²                     i.v.                                      d 0 –3

 

            Course 4

Cytarabine                     25 mg/m²                  s.c. or i.v. every 61               d 0 –4

Daunorubicin                30 mg/m²                   i.v.                                        d 0

Etoposide                      150 mg/m²                 b.i.d. i.v.                               d 0 – 3

Thioguanine                  50 mg/m²                   p.o. every 12 h                    d 0 – 4

Dexamethasone             2 mg/m²                    p.o. every 8 h                      d 0 – 3

           

            Literature:

                        WELLS et al, Curr. Oncol. Rep. 2 (2000): 524 – 528

                        WOODS et al, Blood 87 (1996): 4979 – 4989 and Blood 97 (2001): 56-62

 

2.4.3        Study AML BFM- 87/BFM-93

Induction with either ADE or AIE

 

ADE

Cytarabine                   100 mg/m²               i.v. (cont inf)                      d 1 + 2 and

                                    100 mg/m²               b.i.d. i.v. (30 min inf)         d 3 – 8

Daunorubicin               30 mg/m²                b.i.d. i.v. (30 min inf)         d 3 – 5

Etoposide                     150 mg/m²              i.v. (2 h inf)                        d 6 – 8

 

 

24                                                                                                               Acute Myeloid Leukemia (AML)

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            AIE

Cytarabine                     100 mg/m²              i.v. (cont inf)                       d 1 + 2 and

                                       100 mg/m²              b.i.d. i.v. (30 min inf)         d 3 – 8

Idarubicin                       12 mg/m²                i.v. (30 min inf)                  d 3 – 5

Etoposide                       150 mg/m²              i.v. (2 h inf)                         d 6 - 8

            Patients treated with idarubicin had better blast cell reductions in the bone marrow on day 15,

            However, probabilities of 5 – year EFS and DFS were similar.

 

            In high-risk patients followed by

           

            HAM 

Cytarabine                    3000 mg/m²              b.i.d. i.v.                          d 1 – 3

Mitoxantrone               10 mg/m²                    i.v.                                  d 4 – 5

            Followed by consolidation after hematologic recovery. When on day 15 ≥ 5% of blasts in the bone        marrow, consolidation is started without delay, clinical condition of the patient permitting.

           

            Consolidation (6 weeks)

Prednisone                        40 mg/m²               p.o.                              d 1 – 28

                                         (starting dose)

Thioguanine                      60 mg/m²              p.o.                             d 1 – 28

Vincristine                       1.5 mg/m²               i.v.                                 d 1, 8 , 15, 22

                                          (max 2 mg)

Doxorubicin                      30 mg/m²             i.v.                                d 1, 8, 15, 22

Cyclophosphamide            500 mg/m²           i.v.                                d 29 – 43

Cytarabine                         75 mg/m²             i.v.                                x 16 and

                                           20 – 40 mg*        i.th.

Brain irradiation                12 – 18 Gy**

  *  Age dependent (< 1 year 20 mg ; ≥ 1-2 years 26 mg : ≥ 2 –3 years 34 mg: ≥ 3   

      years 40 mg)

**  Age dependent (< 1 year 12 Gy ; ≥ 1-2 years 15 Gy: ≥ 2  years 18 Gy)

 

Late intensification (2 blocks)

Cytarabine                   3000 mg/m²                  b.i.d. i.v. (3 h inf)                 for 3 d

Etoposide                    125 mg/m²                    i.v. (1 h inf)                           d 2 - 5

 

      Maintenance

Thioguanine               40 mg/m²                 p.o.                            daily

Cytarabine                 40 mg/m²                  s.c.                            d 1 – 4 every 4 wks

For a total of 18 months ( in children with continuous CR). CNS prophylaxis with cytarabine i.th ; CNS irradiation in patients with initial CNS leukemia.

 

Literature:

      CREUTZIG et al, J. Clin. Oncol. 11 (1993): 279 – 286 and J. Clin. Oncol. 19        

      (2001): 2705-2713