Acute Leukemias - Republican Scientific Medical Library

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a 15.4 · Current Treatment of Newly Diagnosed L 3ALL in Adults 193 or “lymphoma regimens” combining relatively moderate doses of cyclophosphamide (CPM), ANTHR, VCR, and PR plus “conventional” CNS prophylaxis, that could cure localized BL, were not sufficient to eradicate systemic and CNS disease in disseminated BL and L 3ALL [27–30] (HD MTX, 3 g/m 2 ). Several groups then showed that considerable improvement in the outcome of disseminated BL and L 3ALL in children could be obtained. The St. Jude’s group, French SFOP, and German BFM group introduced treatment protocols that included, in particular, fractionated high doses of CPM (or ifosfamide), intermediate or high dose (HD) methotrexate and Ara C, and VM26 or VP16 in addition to doxorubicin and VCR (Tables 15.1, 15.2). Very early CNS treatment, with repeated intrathecal therapy and CNS irradiation (which could often be replaced by courses of HD-MTX at 3 g/m 2 ) was added to reduce the incidence of CNS disease. Those groups also showed that, in order to reduce the risk of potentially lethal tumor lysis syndrome, treatment had to start by a small dose (“prephase,” generally combining CPM, VCR, and PR), high-dose chemotherapy being usually started 1 week later. The combination of urate oxidase with induction therapy can also reduce the risk of severe renal injury during early phase of induction therapy [31]. With these intensified protocols, and introduction of a treatment prephase, the prognosis of stage III and stage IV BL had greatly improved, 70–75% of the patients achieving cure. This large pediatric experience also showed that virtually no relapse occurred after 1 year of diagnosis. However, patients with CNS involvement and L 3ALL still had poor outcome using such protocols and had many relapses involving in particular the CNS, and finally cure rates of only 20–30%. This led to start approaches using further intensification of CNS treatment with HDMTX (at 5 g/m 2 in BFM trials and 8 g/m 2 in SFOP trials), a greater number of triple intrathecal injections (with AraC, MTX, hydrocortisone), consolidation with VP16 and HD Ara C, and cranial irradiation [28, 32, 33]. With those protocols, about 75% of BL with CNS involvement and L 3ALL could be cured in the experience of the French SFOP and the German BFM group. Those results were recently confirmed by a UK group, using a SFOP protocol [34]. 15.4 Current Treatment of Newly Diagnosed L 3ALL in Adults The approaches that showed improved results in children were rapidly proposed to adults. In particular, the SFOP and BFM protocols were applied to adults, with no or minor modifications (Tables 15.1, 15.2). Groups involved in the treatment of adult ALL also used the bases of those protocols to adapt their treatment of L 3ALL. Results of the published experience with such treatments are shown in Table 15.3. Application of those reinforced protocols to adult L 3 ALL rapidly led to improved results. For example, all the seven adult L 3ALL patients treated by our group from 1981 to 1984 with conventional (or with slightly reinforced CNS prophylaxis) ALL protocols died within 1 year of diagnosis [18]. By contrast, six of the nine subsequent adult L 3ALL cases, treated by SFOP 86 protocol, were cured of their disease. Favorable results of SFOP programs, especially SFOP 86 protocol in adult L 3ALL, were more recently confirmed by Soussain et al. in 24 patients [35]. Nineteen of them achieved CR, and 14 of them were alive in prolonged first CR. Importantly, eight of the 18 patients who achieved CR in that series were allografted (six cases) or autografted (two cases) in first CR. Three of them died from toxicity, two relapsed and only three were cured of their disease. By comparison, all the 11 patients consolidated with chemotherapy alone remained disease free. This transplantation series may have had especially poor results, notably when compared with a previous French series of allogeneic BMT performed in first CR in adult BL with initial CNS and/or marrow involvement, where seven of nine patients had favorable outcome [36]. Still, results of Soussain, et al. and the recent EBMT series [37] suggest that intensification with an allo or autograft is not justified in L 3ALL in first CR. Pees et al. [38] and Todeschini et al. [39] also applied childhood BL and L3ALL trials to adults (BFM-NHL and POG protocols, respectively) with favorable results, although on smaller numbers of cases. POG 86 trial consists of six courses alternating a cycle A and a cycle B, which are largely similar to BFM-NHL trials, but include, like SFOP 86 trial, HDAraC. Magrath et al. [33] also found that adults with disseminated BL treated with a childhood BL protocol that included the same drugs at similar doses as BFM and SFOP trials achieved as favorable results as with children.
194 Chapter 15 · Burkitt’s <strong>Acute</strong> Lymphoblastic Leukemia (L 3ALL) in Adults Table 15.1. Principles of SFOP Protocols 84 and 86 Prephase: COP COPADM 1 COPADM 2: idem but CYM 2 courses VCR 1 mg/m 2 CPM 300 mg/m 2 MTX (CIT) PRED 60 mg/m 2 (in 2 fractions) VCR 2 mg/m 2 (max. 2 mg) d1 CPM 500 mg/m 2 /d (in 2 fractions) d2 to d4 ADR 60 mg/m 2 d2 HDM 3 g/m 2 d1 MTX (IT) d1 and d6 PRED 60 mg/m 2 (in 2 fractions) d1 to d6 VCR d1 and d6 CPM 1 g/m 2 /d d2 to d4 HD MTX 3 g/m 2 d1 MTX (IT) d2 Ara-C cont. inf. 100 mg/m 2 /d d2 to d6 Ara-C (IT) Sequence 1 d6 – VCR 2 mg/m 2 (max. 2 mg) d1 – CPM 500 mg/m 2 – ADR 60 mg/m 2 d2 – HD MTX 3 g/m 2 d1 – MTX + (IT) d2 – PRED 60 mg/m 2 Sequence 2 (SFOP 86 only) (in 2 fractions) d1 to d6 – ARA C 100 mg/m 2 /d d1 to d5 – VP 16 150 mg/m 2 /d d1 to d5 The German adult ALL group experience of intensified treatment of L3ALL currently remains the largest published in this disorder. Hoelzer et al. [9], who had observed no cure in nine L 3ALL patients treated with a conventional ALL trial, subsequently decided to start d1 and d2 In SFOP 84 trial, treatment is stopped after the first sequence 1. In SFOP protocol 86, CYM courses were replaced by 2 CYVE courses: Ara C 3 g/m 2 /d d2 to d5 and VP16: 200 mg/m 2 /d d2 to d5 and cranial irradiation. Patients received four maintenance courses alternating sequence 1 and 2. Subsequent trials (SFOP 89 and SFOP 95) followed the same approach with relatively minor changes, intermediate risk patients receiving an LMB 84 type protocol, and high risk patients (including L3ALL) receiving an LMB 86 type protocol. a specific L 3 trial (B-NHL83) which, like the SFOP and BFM trials, included a prephase, followed by repeated cycles with intermediate dose MTX, fractionated CPM and VCR (Table 15.4). The CR rate was 63%, and 47% of the patients who had achieved CR relapsed. Relapses
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E.H. Estey · S.H. Faderl · H. M.
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E. H. Estey Department of Leukemia
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VI Table of Contents 14 Philadelphi
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VIII Contributors S. H. Faderl Depa
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X Contributors D. Wartenberg Depart
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Therapy of AML Elihu Estey Contents
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a 1.2 · Standard Therapy 3 Table 1
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a 1.2 · Standard Therapy 5 Table 1
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a 1.2 · Standard Therapy 7 tween G
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a 1.2 · Standard Therapy 9 Fig. 1.
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a 1.2 · Standard Therapy 11 of tre
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a 1.2 · Standard Therapy 13 Table
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a 1.2 · Standard Therapy 15 permit
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a References 17 19. Care RS, Valk P
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a References 19 6-thioguanine in th
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Acute Myeloid Leukemia: Epidemiolog
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a 3.1 · Epidemiology 49 3.1.4 Gend
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a 3.2 · Etiology 51 part of the in
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a 3.2 · Etiology 53 for the develo
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a References 55 38. Crane MM, Stom
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Relapsed and Refractory Acute Myelo
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a 4.2 · Prognostic Factors in Pati
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a 4.3 · Treatment of Relapsed and
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a 4.4 · Hematopoietic Stem Cell Tr
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a 4.6 · Gemtuzumab Ozogamicin 65 T
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a 4.7 · Relapsed and Refractory Ac
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a 4.7 · Relapsed and Refractory Ac
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a References 71 The ability of immu
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a References 73 39. Vogler WR, McCa
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a References 75 95. Sievers EL, Lar
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Part II - Acute Lymphoblastic Leuke
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78 Chapter 5 · Acute Lymphoblastic
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Molecular Biology and Genetics Meir
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a 6.3 · Structural Aberrations 97
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a 6.3 · Structural Aberrations 99
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a 6.5 · Molecular Aberrations 101
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a References 103 clear that homozyg
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a References 105 53. Chim CS, Tam C
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a References 107 122. Lennard L, Li
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Diagnosis of Acute Lymphoblastic Le
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a 8.3 · Cytochemistry and Immunoph
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a 8.5 · Cytogenetic and Molecular
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a 8.5 · Cytogenetic and Molecular
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a References 127 including the reti
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a References 129 47. Kita K, Shirak
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Acute Lymphoblastic Leukemia: Clini
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a 7.3 · Diagnosis 111 or neoplasti
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a 7.3 · Diagnosis 113 Fig. 7.2. Hi
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a 7.3 · Diagnosis 115 The vast maj
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a References 117 dren: Biologic bas
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General Approach to the Therapy of
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a 9.3 · New Agents 133 dose methot
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a References 135 4. Gökbuget N, Ho
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138 Chapter 10 · Recent Clinical T
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244 Chapter 19 · Novel Therapies i
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246 Chapter 19 · Novel Therapies i
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248 Chapter 20 · Minimal Residual
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276 Chapter 22 · Relapsed Acute Ly
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278 Chapter 22 · Relapsed Acute Ly
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Emergencies in Acute Lymphoblastic
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a 23.5 · Hyperleukocytosis 283 LA
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a 23.9 · Neurological Complication
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a References 287 29. Hingorani AD,
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Subject Index A aberrant methylatio
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a Subject Index 291 CREB, see enhan
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a Subject Index 293 MUD, see matche
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