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230  /  Chapter 17  Acute lymphoblastic leukaemia



                   Induction                               100
                   e.g. vincristine, asparginase,                      96±3
                                                          Probability of overall survival (%)
                      dexamethasone (or prednisolone)  ± daunorubicin  80  84±2
                   Consolidation                                                 81±2  74±2
                   e.g. daunorubicin, cytosine arabinoside, vincristine,   60
                      etoposide, thioguanine or mercaptopurine,
                      cyclophosphamide in one to four courses  40                              48±2
                                   Possible stem cell
                                   transplantation          20
                   Cranial prophylaxis
                   e.g.  high dose systemic methotrexate                                          21±4
                      or multiple intrathecal methotrexate   0
                      or cranial irradiation (1800–2400 rad)   0      10       20       30      40
                      + intrathecal methotrexate
                                                                           Years after diagnosis
                                                                       Studies 1 to 4, 1962–1966
                   Maintenance therapy                                 Studies 5 to 9, 1967–1979
                   e.g. mercaptopurine, methotrexate, vincristine,     Study 10, 1979–1983
                      dexamethasone (or prednisolone)                  Studies 11 and 12, 1984–1991
                                                                       Studies 13A, 13B and 14, 1991–1999
                                                                       Study 15, 2000–2010
                   Late intensification (as consolidation)
                                                         (b)
                   Maintenance therapy as above (2–3 years)
                   (a)

                              Figure 17.6   Acute lymphoblastic leukaemia (ALL).  (a)  Flow chart illustrating typical treatment regimen.

                      (b)  Kaplan – Meier analyses of overall survival in 2628 children with newly diagnosed ALL.  (Updated from
                    Pui C.H. and Evans W.E. (2006)  N Engl J Med   354 , 169  .)

                              Normal BM                 ALL diagnosis              ALL remission





                        CD10 PE                    CD10 PE                    CD10 PE

                                       CD34 PerCP   CD38 FITC     CD34 PerCP   CD38 FITC     CD34 PerCP


                         CD38 FITC
                                                          CD19 APC

                              Figure 17.7   Detection of minimal residual disease (MRD) by four - colour fl ow cytometry in: normal bone marrow


                    mononuclear cells (BM), BM from a patient with B lineage ALL at diagnosis and in remission 6 weeks after
                    diagnosis. The cells were detected with four different antibodies (anti - CD10, anti - CD19, anti - CD34, anti - CD38)
                    attached to fl uorescent labels abbreviated as PE, APC, PerCP and FITC, respectively. The tridimensional plot
                                                 +
                    shows the immunophenotype of CD19   lymphoid cells in the three samples. MRD of 0.03% of cells expressing
                                                                −
                                                           +
                                                     +
                    the leukaemia - associated phenotype (CD10  , CD34  , CD38  ) were detected at 6 weeks, confi rmed by polymer-
                    ase chain reaction (PCR) analysis.  (From Campana D. and Coustan - Smith E. (1999)  Commun Clin Cytometry
                      38 , 139 – 52, with permission.)
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