Acute Leukemias - Republican Scientific Medical Library

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a 16.8 · Results of Stem Cell Transplantation in LBL 209 patients. Therefore MedRad still has a role in adult LBL. Since an irradiation dose of 24 Gy may not be sufficient in the new GMALL protocol for T-LBL, patients receive prophylactic MedRad at a dose of 36 Gy similar to the dose included in NHL protocols for local irradiation. Irradiation is delivered after induction therapy without parallel chemotherapy in order to reduce hematotoxicity. On the other hand, MedRad leads to delays of systemic chemotherapy and since hematopoietic tissue is involved, toxicity of subsequent chemotherapy cycles may be increased. Due to this dilemma the optimal strategy remains to be defined. 16.7 Prognostic Factors One important issue in adult LBL is the identification of prognostic factors in order to define indications for SCT in first CR. A variety of risk factors for relapse have been described in single studies such as higher age (>30– 40 years) [12, 14, 15, 30, 42], increased LDH (either above normal or above 2´ normal) [11, 12, 14, 15, 21, 23], CNS [12, 18, 23, 30], bone marrow [12, 23, 24, 42, 43] or extranodal involvement [21], stage IV disease [12, 15, 23, 42, 43], presence of B-symptoms [14], or decreased hemoglobin [14]. The majority of them are indicators for advanced disease or large tumor mass. Partial or late response was also associated with a poorer outcome [11, 14, 30]. Both recent larger trials with intensive chemotherapy hardly identified prognostic factors in adult LBL. In the GMALL series on T-LBL, the only significant prognostic factor for survival was elevated LDH. No single risk factor for relapse risk could be identified. Particularly the stage of disease and age did not have a prognostic impact [11]. In the MDACC series only CNS involvement at diagnosis was significantly associated with poorer outcome [18]. Similarly no prognostic factors were identified in the largest series in childhood T-LBL. Neither age, stage, LDH, nor immunophenotype appeared to have an impact on DFS [7]. The decreased relevance of single prognostic factors may therefore be a consequence of more effective chemotherapy in adult as well as in childhood LBL. A convincing prognostic model has not yet been defined for adult LBL. New prognostic factors are required to define indications for SCT in CR1. The better characterization of biologic markers, e.g., immunophenotype of T-LBL, may contribute to this aim. Rational assessment of individual treatment response and relapse risk may be based on evaluation of minimal residual disease from bone marrow or peripheral blood. Furthermore, analysis of gene expression profiles, as recently published for T-ALL [44] and T-LBL [4], may help to identify new prognostic markers in T-LBL. 16.8 Results of Stem Cell Transplantation in LBL SCT was included to a different extent in published studies and sometimes restricted to high risk LBL patients (Table 16.4). 16.8.1 Autologous SCT The majority of studies evaluated the role of autologous (auto) SCT with a weighted mean for DFS of 61 (31–77)% [13–16, 45–47, 49, 50]. One prospective study was based on treatment with two sequential high-dose induction courses (without HDAC or HDMTX) followed by BEAM and autologous SCT. Thirteen patients with LBL were included and the CR rate was 73%. At 5 years the survival was 46% and the DFS 40%, which is inferior to chemotherapy studies. Surprisingly, results with this regimen were significantly better in Burkitt’s lymphoma [52]. This favorable result for auto SCT in de novo and advanced disease may be at least partly due to selection mechanism, e.g., part of the patients reaching auto SCT after intensive front-line therapy may have been already cured by chemotherapy and the few patients reaching auto SCT after relapse of LBL may represent those few with chemosensitive disease at relapse. 16.8.2 Allogeneic SCT Less experience exists with allogeneic (allo) SCT in LBL [16, 45, 50] with a mean DFS of 74 (59–91%) in a few small series (Table 16.4). In a survey of the European Bone Marrow Transplantation Registry (EBMTR), the survival of 222 LBL patients with allo SCT in first remission or advanced disease was 38% with a considerable rate of transplant related mortality (TRM) (31%). In this
210 Chapter 16 · Treatment of Lymphoblastic Lymphoma in Adults Table 16.4. Results of SCT in lymphoblastic lymphoma Author Auto CR1 Year N DFS Milpied, et al. [45] 1989 13 68% a Baro, et al. [46] 1992 14 77% Morel, et al. [14] 1992 5 60% b Bouabdallah, et al. [16] 1998 16 62% b Verdonck, et al. [47] 1992 9 67% b Santini, et al. [13] 1991 21 66% Sweetenham, et al. [48] 1994 105 63% c Jost, et al. [42] 1995 17 31% d Zinzani, et al. [15] 1996 10 70% b Conde, et al. [49] 1999 58 76% Sweetenham,et al.[50] 2001 31 55% Song, et al. [34] 2007 25 69% Total Auto > CR1 241 61 (31–77)% Baro, et al. [46] 1992 8 50% Morel, et al. [14] 1992 7 43% b Conde, et al. [49] 1999 11 36% Total Allo CR1 15 47 (43–50)% Milpied, et al. [45] 1989 12 68% a Bouabdallah,et al. [16] 1998 11 91% b Sweetenham, et al. [50] 2001 7 59% Total 30 74 (59–91)% Allo > CR1 Morel, et al. [14] 1992 7 14% b Van Besien, et al. [51] 1996 25 17% Total 32 16 (14–17)% According to [11] a for allo and auto together; no difference observed b percentage, not probability c overall survival d including Burkitt’s lymphoma study the lower relapse rate after allo SCT was outweighed by higher mortality [53]. 16.8.3 Auto Versus Allo SCT In several reports, results of auto and allo SCT were compared. Milpied, et al. reported a series of 25 patients with stage III-IV LBL. The LFS was 68% with no difference between allo and auto SCT [45]. Another group reported results of allo SCT in LBL which was performed in younger patients with advanced disease. Ten out of 12 patients mainly transplanted in CR1 survived disease free. LFS after allo SCT was superior (78%) to auto SCT (50%) in this study [16]. Results of SCT (auto N = 128; allo N = 76) in 204 LBL patients at different stages of disease are available from an analysis performed by the International Bone Marrow Transplantation Registry (IBMTR) and the Autologous Blood and Marrow Transplantation Registry (ABMTR). Not surprisingly, there was a higher TRM after allo (18%) compared to auto (3%) SCT. On the other hand, the authors observed a lower relapse rate of 34% for allo compared to 56% for auto SCT after longer observation time. Altogether there was no difference of survival at 5 years with 44% for auto and 39% for allo SCT. Prognostic factors for DFS were donor source, BM involvement, and disease stage [54]. As these are registry data, the options for interpretation are limited. The overall result is not superior to chemotherapy, but includes patients with advanced disease. The risk profile of the patients and the effects of previous therapy, which may be particularly important for auto SCT, are not analyzed. However, there seems to be a graft-versuslymphoma effect in LBL. Since TRM may be lowered in more recent trials, allo SCT could be an option for high-risk T-LBL. In patients after relapse allo SCT should probably be preferred to auto SCT in patients with an available donor. 16.8.4 Auto SCT Versus Chemotherapy In the largest prospective trial with randomized comparison of auto SCT and conventional consolidation/maintenance, however, only 65 of 98 eligible patients were actually randomized. The DFS for conventional chemotherapy was 24% compared to 55% for auto SCT. No difference was detected for survival (45 vs. 56%).
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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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146 Chapter 11 · Conventional Ther
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260 Chapter 20 · Minimal Residual
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262 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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