Acute Leukemias - Republican Scientific Medical Library

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170 Chapter 13 · Treatment of Adult ALL According to Protocols of the German Multicenter Study Group for Adult ALL (GMALL) Table 13.2. Results of the GMALL Trial 05/93 [5] SR HR Elderly T-ALL Evaluable 291 352 216 304 CR 87% 85% 70% 86% Early death 50 years) the GMALL study group decided to initiate a trial with dose-reduced chemotherapy for older patients (> 55–65 years according to biological age). 13.2.3 Study 06/99 and 07/03 The GMALL study 06/99 was initiated as a pilot trial. One major aim was to develop a new, shortened, and intensified induction regimen based on the following new principles compared to previous GMALL trials: (1) Dexa- VHR, very high risk; SCT, stem cell transplantation; auto, autologous; allo, allogeneic; MUD, matched unrelated. methasone (DEXA) instead of prednisone to improve antileukemic activity and prophylaxis of CNS relapse; (2) prephase with CP; (3) G-CSF parallel to chemotherapy; (4) intensified daunorubicin with two 2-day cycles (DNR) vs. 4 weekly applications; and (5) one dose PEG- L-ASP instead of 14 days conventional ASP. Induction I was followed by GMALL induction phase II as previously reported (Fig. 13.2) and a uniform consolidation I. Thereafter treatment was risk adapted. Patients with HR features and with very HR ALL (Ph+) were transferred to SCT in first CR including allogeneic sibling, matched-unrelated, and autologous SCT. Patients with SR ALL received six consolidation cycles and a reinduction therapy. Maintenance therapy was stratified according to the course of minimal residual disease (MRD) (see below). Figure 13.3 gives an overview on the study design. Overall, 843 patients with a median age of 36 years were included. The CR rate was 83%, with 12% failure/ PR and 7% early death (ED). The CR rate improved after
a 13.3 · Therapy of Ph/BCR-ABL-Positive (Ph+) ALL 171 Fig. 13.4. Development of high-risk features in the GMALL studies. modifications of the DEXA regimen. With lower doses of DEXA, the rate of ED and severe infections decreased significantly. The earlier application of G-CSF during phase I of induction contributed to a significant decrease of grade III/IV granulocytopenias and probably also mucositis [6]. The optimized regimen for induction (Fig. 13.2) was used in the ongoing study 07/03. Interim results confirmed the high antileukemic activity with CR rates of 89% and the feasibility with 4% ED. Beside the optimized induction, the use of Imatinib in Ph+ ALL parallel to induction (see below) contributed to the improvement. Further progress is attempted by additional use of rituximab in CD20-positive patients. The aim of this trial is to improve overall survival (OS) to above 50%, and according to interim results this goal seems to be achievable. 13.2.4 Results of Stem Cell Transplantation The general principle was to administer allogeneic SCT in CR1 only for HR patients (definition Fig. 13.4) starting with study 04/89. Patients with Ph+ ALL were also eligible for matched, unrelated BMT (starting with study 05/93). Starting with study 06/99 sibling and unrelated SCT were used on an equal footing. In GMALL study 05/93 survival after SCT in CR1 in HR patients was 34% for sibling (n = 68) and 51% for unrelated donors (n = 31). The most favorable results for sibling SCT were obtained in pro-BALL (59%). In Ph+ ALL, unrelated SCT improved survival (50%) compared to sibling SCT (25%) [7]. Equal survival rates for matched related (45%) or unrelated (42%) SCT in 1 st CR were also reported from an overview analysis of nine German SCT centers [8]. In the GMALL study 06/99, also high-risk T-lineage ALL patients were candidates for SCT in CR1. The OS after sibling SCT (n = 50) was 53% and after unrelated SCT (n=71) 44%. Results of SCT differed significantly between the subgroups ranging from 74% in ProB and 64% in HR-T-ALL to 44% in Ph+ALL and 18% in HR- B-lineage ALL. Thus it could be demonstrated that pro B-ALL and HR T-ALL profit substantially from allogeneic SCT. The results for Ph+ALL were promising and underlined the value of MUD SCT. HR-B-lineage ALL did poorly with chemotherapy alone as well as with SCT [9]. 13.3 Therapy of Ph/BCR-ABL-Positive (Ph+) ALL Treatment of this formerly most unfavorable subtype was revolutionized by the invention of imatinib as the first therapy targeted to the increased tyrosine-kinase (TK) activity induced by the bcr-abl rearrangement. An early phase II trial in relapsed/refractory Ph+ ALL demonstrated a CR rate of 29% [10]. Resistance and relapse developed rapidly in the majority of patients, although a proportion of patients could be transferred to allogeneic SCT [11]. It could be demonstrated furthermore that treatment response was significantly correlated to the quantitative course of BCR-ABL levels in
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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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Page 143 and 144: ALL Therapy: Review of the MD Ander
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Page 149 and 150: Treatment of Adult ALL According to
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222 Chapter 17 · The Role of Allog
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230 Chapter 18 · The Role of Autol
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238 Chapter 19 · Novel Therapies i
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248 Chapter 20 · Minimal Residual
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264 Chapter 21 · Central Nervous S
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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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