AcuteMyeloidLeukemia(AML)                                                                                                       15

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2.   Acute Myeloid Leukemia (AML)

 

2.2.                             Younger adult patients ( < 60 years)

 

2.2.1                              Induction treatment

 

2.2.1.1                       “ 7+3 ” ( “ 3+7 ” )

Daunorubicin                           45 – 50 mg/m²                       i.v.                           d 1-3 

Cytarabine                                100 – 200 mg/m² /d              i.v. (cont inf)            for 7 d

 

Literature:

            BISHOP et al, Blood 75 (1990): 1-6

            MAYER et al, N. Engl. J. Med. 331 (1994): 896 – 903

            OMURA et al, Cancer 49 (1982): 1530 – 1536

            PREISLER et al, Blood 69 (1987): 1441 – 1449

 

18                                                                                                               Acute Myeloid Leukemia (AML) ____________________________________________________________________________________

 

2.2.1.2                       DAT/TAD ( various modifications)

Literature:

            MAYER, Semin. Oncol. 14 (1987): 384 – 396 (review)

 

E.g. TAD 9

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

Thioguanine                    100 mg/m²               b.i.d. p.o. every 12 h        d 3 – 9

Daunorubicin                   60 mg/m²                i.v. (1 h inf)                       d 3 – 5

 

Literature:

            BάCHNER et al, J.Clin. Oncol. 3 (1985): 1583 – 1589

 

2.2.1.3                       ADE

Daunorubicin                                  50 mg/m²          i.v.                             d 1 , 3 , 5

Cytarabine                                      100 mg/m²        b.i.d. i.v.                     d 1 – 10

Etoposide                                       100 mg/m²         i.v. (1 h inf)                d 1 – 5

 

                        Literature:

                                    HANN et al, Blood 89 ( 1997): 2311 – 2318

 

2.2.1.4                       ICE

Idarubicin                                        10 mg/m²           i.v.                           d 1, 3, 5

Cytarabine                                       100 mg/m²         i.v. (cont inf)           d 1 – 10

Etoposide                                        100 mg/m²          i.v.                           d 1 – 5

                       

 

                        Literature:

                                    GORIN et al, Ann. Oncol. 4 (Suppl 1) (1993) : 59 – 80

In a systematic collaborative overview of randomized trials induction regimens based on idarubicin achieved better remission rates and better overall survival than those based on daunorubicin.

 

Literature:

            THE AML COLLABORATIVE GROUP, Br. J. Haematol. 103 (1998): 100 – 109

 

2.2.1.5                       HAM

Cytarabine                         3000 mg/m²           b.i.d. i.v. (3 h inf)                  d 1 – 3

Mitoxantrone                     10 mg/m²               i.v. (30 min inf)                     d 3 – 5

 

                        Literature:

                                    HIDDEMANN et al, Blood 69 (1987): 744 – 749

                                    KERN et al, Leukemia 12 (1998): 1049 – 1055 (superiority of            

                                    high- dose over intermediate- dose cytarabine in prospective  

                                    randomized comparison)

 

2.2.1.6                       FLAG

Especially for poor prognosis AML, e.g. with multiline age dysplasia

Fludarabine                       30 mg/m²              i.v. (30 min inf)        d 1 – 5

Cytarabine                        2000 mg/m²          i.v.                            d 1- 5 (3-5 h after

                                                                                                           fludarabine)

G- CSF                             300 ΅g          s.c.                                    daily form d 0 to

                                                                                                      achievement of CR

 

 

 

 

Acute Myeloid Leukemia (AML)                                                                                                       19

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                        Literature:

                                    FERRARA et al, Eur. J. Haematol. 68 (2002): 203 – 209

 

2.2.1.7                       Double induction

As a very early intensification; e.g. TAD – TAD (see 2.2.1.2) or TAD- HAM (see 2.2.1.2 and 2.2.1.5) (especially for poor- risk patients).

 

Literature:

            BάCHNER et al, Blood 93 (1999): 4116 – 4124

 

2.2.2                              Post remission therapy

To prevent relapses, three options of further intensive treatment are available

 

2.2.2.1                       Chemotherapy

Aggressive approaches including high- dose cytarabine are preferred over long term

maintenance  therapy of median or low intensity, but the optimal regimen, number of doses per course, and number of courses is still not defined.

 

Literature: e.g.

        BάCHNER et al, Int. J. Hematol. 72 (2000): 285 – 289

        BYRD et al, J. Clin. Oncol. 17 (1999): 3767 – 3775

        CASSILETH et al, N. Engl. J. Med. 339 (1998): 1649 – 1656

        PALMIERI et al, Leuk. Res. 26 (2002): 539 – 543

 

2.2.2.2                       Allogeneic stem cell transplantation

Literature: e.g.

        APPELBAUM, Leukemia 14 (2000): 497 – 501

        BURNETT, Cancer Chemother. Pharmacol.48 (Suppl 1) (2001):53-

        58(review of the contribution of allogeneic and autologous        

        transplantation)

        BURNETT et al, Lancet 351 (1998): 700 – 708 (randomized  

        comparison of addition of autologous bone marrow transplantation to   

        intensive chemotherapy: study MRC AML 10)

                                CASSILETH et al, N. Engl. J. Med. 339 (1998): 1649 – 1656  

                                (chemotherapy Compared with autologous or allogeneic bone  

                                marrow transplantation :US Intergroup study)

                                COUBAN et al, Blood 100 (2002): 1525 – 1531 (randomized  

                                multicenter comparison of bone marrow and peripheral blood  

                                allogeneic transplantations for myeloid malignancies)

                                FOUILLARD et al, Blood 100 (2002): 3135 – 3140 (EBMT study of  

                                hematopoietic stem cell transplantation for de novo erythroleukemia)

                                RINGDEN et al, J. Clin. Oncol. 20 (2002): 4655 – 4664 (comparison

                                of peripheral blood stem cells with bone marrow)

                                TALLMAN et al, Blood 96 (2000): 1254 – 1258 (effect of  

                                postremission Chemotherapy before allogeneic transplantation)

                                ZITTOUN et al, N. Engl. J. Med. 332 (1995): 217 – 223 (autologous

                                or allogeneic bone marrow transplantation compared with intensive

                                chemotherapy: EORTC – GIMEMA study)

 

 

20                                                                                                               Acute Myeloid Leukemia (AML) ____________________________________________________________________________________

 

2.2.2.3                       Autologous stem cell transplantation

Literature: e.g.

            BURNETT, Cancer Chemother. Pharmacol. 48 (Suppl 1) (2001): 53 – 58 (review of

            the contribution of allogeneic and autologous transplantation)

            CASSILETH et al, N. Engl. J. Med. 339 (1998): 1644 – 1656 (chemotherapy

            compared with autologous or allogeneic bone marrow transplantation: US

            Intergroup study )

            HAROUSSEAU et al, Blood 90 (1997): 2978 – 2986 (comparison of autologous

            bone marrow transplantation and intensive chemotherapy)

            LEVI et al, Blood 98 (Suppl) (2001): 202b, abstr, 4514 (meta- analysis of autologous bone marrow transplantation vs chemotherapy)

            ROHATINER et al, Ann. Oncol. 11 (2000): 1007 – 1015

            ZITTOUN et al, N. Engl. J. Med. 332 (1995): 217 – 223 (autologous or allogeneic      bone marrow transplantation compared with intensive chemotherapy:

            EORTC – GIMEMA study)

 

2.2.3                              Salvage therapy

A number of newer agents has shown activity in recurrent AML, Including amsacrine, mitoxantrone, high–dose cytarabine, fludarabine, troxacitabine, homoharrigtonine, diaziquone, idarubicin, topotecan, and etoposide, some of these agents are being used in combination regimens, e.g.

 

2.2.3.1                       S – HAM         

Cytarabine             500*-1000 mg/m²           b.i.d. i.v. (3h inf)          d 1 , 2, 8 , 9

Mitoxantrone         10 mg/m²                        i.v. (30 min inf)           d 3 , 4 , 10 ,11

G- CSF                                                          starting                        d 14

     *   In older patients

 

      Literature

            KERN et al,  Cancer 79 (1997): 59 – 68

 

 

2.2.3.2                       FLAG       

Fludarabine              25 – 30 mg/m²                   i.v.                            d 1 – 5

Cytarabine               2000 mg/m²                       i.v.                            d 1, 2, 8, 9

G- CSF                     300 - 400΅g                        s.c. until hematopoietic recovery

     

 

            Literature:

            FERRARA et al, Ann. Hematol. 78 (1999): 380 – 384

                        MONTILLO M et al, Am. J. Hematol. 58 (1998): 105 – 109

                        VISANI et al, Leukemia 8 (1994): 1842 – 1846

 

2.2.3.3.                     CAT

         

Cyclophosphamide               500 mg/m²                   b.i.d. i.v.                       d 1– 3

Topotecan                            1.25 mg/m²                  i.v. (cont inf)                 d 2- 6

Cytarabine                           2000 mg/m²                 i.v.(4 h inf)                    d 2- 6

            To be repeated every  3 – 4 weeks ( Provided there was full recovery from prior  

            toxicity)

 

             Literature:

                     CORTES et al, Leuk Lymph. 36 (2000): 479 – 489

 

 

 

Acute Myeloid Leukemia (AML)                                                                                                       21

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2.2.3.4                          Marrow-ablative (high-dose) cytotoxic treatment followed by hematopoietic stem cell

               transplantation (autologous or allogeneic)

               The details of these procedures are outside of the scope of this short

                compilation.

 

             Literature :

                        BROWN et al, Blood 85 (1995): 1391-1395 (allogeneic transplantation in  

                        untreated first relapse)

                        CLIFT et al, J. Clin. Oncol. 10 (1992): 1723-1729 (allogeneic  

                        transplantation in untreated first relapse)

                        CHOPRA et al , J. Clin. Oncol. 9 (1991): 1840-1847 (autologous bone

                        marrow transplan-

                        tation beyond first remission)

                        MICHALLET et al. Bone Marrow Transplant. 26 (2000): 1157-1163

                        PETERSEN et al. J. Clin. Oncol. 11 (1993): 1353-1360 (autologous bone 

                        marrow transplantation in untreated first relapse or in second CR)