1. Adult ALL – therapeutic strategies, including Burkitt
and Lymphoblastic Lymphomas
D.Hoelzer
J.W.Goethe University
Frankfurt
for the GMALL Study Group
German Multicenter Studies for Adult Acute Lymphoblastic Leukemia
Caesarea, April 2008 1

2. Comprehensive Therapeutic Strategy in Acute Lymphoblastic Leukemia
MRD evaluation
2. New „targeted“ therapies e.g. Ph+ ALL
3. Antibody Therapy e.g. B-ALL/Burkitt NHL
4. Stem cell transplantation
5. New cytostatic drugs
6. Treatment of subentities and related diseases e.g. Elderly, Adolescents, T-LBL

3. Methods and Definition of Minimal Residual Disease (MRD)
in Acute Lymphoblastic Leukemia
= leukemic blast cells undetectable by microscopic examination of bone marrow
(<1-5% blast cells)
Definition of Mol. CR ≤ 0,01% = ≤1 LBC in
Methods of detection
Flow – 10-3
Mol. Gen. TCR, IHgR
RT PCR (bcr abl)
MRD should be applicable in 95% of ALL pts !
but for technical reasons lower %

4. Value of MRD for Adult ALL
Induction therapy

5. MRD based German Multicenter Study for Adult ALL – GMALL 07/2003
Overview Plan
Stratification I
According to Risk Factors
Stratification II
according to MRD
(6 TPs)
Intens.
Maint.
MRD SR HR
Stop
SZT
IMR
HD-MTX
ASP I II
ReInduction
VM 26
ARAC
CYCLO
6 MP SR
Molecular
Failure
Induction
Cons. I V
Phase I
Phase II
CNS 24 Gy
Med 24 Gy
SC-
collection HR
VHR
SCT
i.th. Triple
prophylaxis
i.th. MTX 
   
 (HR/VHR)      1 4 5 7 9 11 13 16 19 22 25 27 30 33 36 39 41 43 46 49 51 53
weeks

6. Patientenrekrutierung in laufende GMALL-Studien
de novo N 1921
GMALL 07/
GMALL für ph+ Pat. < 55 J
GMALL mit Rituximab (SR)
GMALL Elderly 1/
GMALL T-LBL 1/
GMALL B-ALL/NHL
Rezidivstudien N 171
Compound 506U78 (AraG) 140
Depocyte für ZNS-Rezidive 19
Campath 12
10/07

7. Results of Recent Trials in Adult ALL
INDUCTION THERAPY
Group Year N Age Drugs Early Death CR
CALGB V,P,D,A,C 8% 85%
LALA (<60) V,P,D/Z,C,[AM/HDAC] 9% 76%
NILG 08/ V,P,I,A,[C] 8% 84%
GMALL 05/ (<65) V,P,D,A,C,AC,MP 7% 83%
JALSG-ALL (<60) V,P,AD,A,C 6% 78%
UCLA (<60) V,P,D,A 1% 93%
Sweden V,BX,D,C,HDAC n.r. 75%
GIMEMA (<60) V,P,D,A,C, [HDAC,Mi] 11% 82%
MD Anderson V,DX,AD,C,HDM,HDAC 5% 92%
EORTC ALL V,P,D,C,[AM/HDAC] n.r. 74%
LALA (<55) V,P,I/D,C 5% 84%
GOELAL02* (<60) V,P,I,A 2% 86%
MRC/ECOG (<60) V,P,D,A,C,AC,MP n.r. 91%
GIMEMA (<60) V,P,D,A n.r. 80%
Pethema ALL-93* (<50) V,D,P,A,C 6% 82%
Netherlands (<67) AC,VP,M - V,DX,AD 9% 88%
JCOG (<64) V,C,P,AD,A 10% 83%
N: 7262
ED: 7% (2-11%)
CR: 84% (74%-93%)
* HR only

8. CYTOLOGIC CR Rate after induction
GMALL Study 07/2003
Total
Eval 713
CR 91%
PR/Fail 6%
ED 5%
Standard High
92% 88%
4% 9%
4% 4%
Very High (Ph+)
119
85% (CH + IMat) 8%
high CR rate for all risk groups !
achievement of hematol. CR important
but no prognostic value for ALL subgroups

9. MOLECULAR CR rate (MRD < 10-4 after induction)
GMALL Study 07/2003
Cyto CR Mol CR N
Total 91% 69%
SR 92%
HR 88%
<35 yrs 90%
>35 yrs 89%
B-precursor 89%
T-ALL 90%
71%
44%
72%
61%
59%
84%

10. Cytologic and Molecular CR
Subtype: B vs T
Survival of CR
Survival of CR
B Mol CR N=82 79%
No Mol CR N=48 37%
T Mol CR N=52 68%
No Mol CR N=14 28%
B-Lin N=525 50%
T-Lin N=202 60%
 B- and T-lineage: need for improvement of Molecular Cr rate

11. Conclusion Molecular CR after induction therapy
New endpoint for effectivity ?
Therapeutic consequences ?
Molecular failure
 Immediate SCT
 New targeted drugs ?
Molecular CR
 SCT still in HR/VHR (Ph+) pts ?
 Proof in randomized studies !

12. Why do we need MRD evaluation in addition to „conventional“ risk factors ?

13. Stratification I: Conventional Prognostic Factors
Risk Stratification
GMALL Study 07/2003
Unfavourable Prognostic Factors
High WBC > /µl in B-precursor
Subtype pro B, early T , mature T
Late CR > 3 Wo (after induction II)
Cytogenetic/ t(9;22) - BCR-ABL
Molecular Aberrations t(4;11) - ALL1-AF4
Complex aberrant karyotype*
Stratification I: Conventional Prognostic Factors
Standard
No Factor
Very High
BCR-ABL
High
 1 Factor
50%
33%
17%
>=3 Aberrationen; mind. 1 Strukturaberration (Ausnahme: >50, t(9;22), 11q23, t(10;14), t(1;19), 8q24, t(14;18), t(11;14)

14. Adult B-Lineage ALL: Leukemia
Free Survival
GMALL Trial 05/93
Standard Risk (n=396)
High Risk (n=245)
Very High Risk (n=152)
55 %
36 %
20 %
MRD
SCT
WKH 06/2004

15. Survival after SCT in HR ALL According to Type of SCT
GMALL Study 07/2003
Allo sibling: 0.54 (N=42)
Allo MUD: 0.55 (N=81)
Auto: 0.56 (N=10)
~ 50% survival for High Risk pts after allo sib / MUD / Auto SCT

16. Time to achieve Molecular Remission in Standard Risk ALL
Kinetics of Mol.CR in B- and T-Lin.ALL
GMALL Studies 06/99 – 07/03
No increase of Mol CR > d 71
Lowest MRD level = best time point for SCT

17. Conclusion MRD in Adult ALL I
Statements mainly based on GMALL 07/2003 experience
1) Molecular CR
after induction therapy of greater prognostic
impact than cytol. CR
2) „Slow“ decrease / dissapearance of MRD in adult
B/T-lin. ALL
compared to children
3) Best time point for MRD decision
week 16 = after ind.+cond.

18. Ph+ ALL Treatment results before the Imatinib era
Imatinib / Chemo / SCT in younger patients
Value of MRD
Imatinib Mono in Elderly
Mutations and resistance
New TK Inhibitors
Dasatinib, Nilotinib, Aurora, others

19. Survival of CR Pts in Ph/BCR-ABL+ ALL
with and without Stem Cell Transplantation
GMALL Study 05/93
Chemo only: (N=88)
Chemo+SCT: 0.30 (N=95)

20. Imatinib in the Treatment of
Adult Ph+ ALL
Questions
Concomitant with intensive induction
therapy ?
Increase in (hemato) toxicity ?
Other toxicities ?

21. DEX, CYP, DNR, VCR, ASP, MP, CYT
Wassmann et al.
(n = 92)
Thomas et al.
(n = 26)
Yanada
et al.
(n = 80)
Lee et al.
(n = 20)
Oriol et al.
(n = 30)
Induction regimen
DEX, CYP, DNR, VCR, ASP, MP, CYT
Hyper-CVAD
CYP, DNR, VCR, PDN
DNR, VCR, PDN, ASP
VCR, DNR, PDN CR
88%
96%
95%
90%
Induction mortality 8% NR
2.5% 5% 7%
Death in remission
16%
15%
10%
PCR neg % % % % n.a.
Thomas, 2004,
abstract;
Towatari, 2004,
preprint, p8,9, 15,
16, 28, 29
Lee, 2005,
p1509, c1, ¶1,
p1511, c2, ¶1;
Oriol, 2005,
EHA abs
Integrating imatinib into standard induction chemotherapy regimens improves outcomes as compared with historical cohorts in newly diagnosed Ph+ ALL.
In addition to adding imatinib to hyper-CVAD, as discussed on the previous slide, promising results have also been obtained by adding imatinib to other intensive regimens used to treat adults with newly diagnosed Ph+ ALL.
Towatari and colleagues from the Japan Adult Leukemia Study Group administered imatinib in combination with their standard age-based intensive chemotherapy regimen to 24 newly diagnosed Ph+ ALL patients (median age, 41.5 years; range years). Imatinib was administered at a dose of 600 mg/d from days 8 to 63 during induction therapy with cyclophosphamide, daunorubicin, vincristine, and prednisolone, then alone for 28 days during second consolidation, and finally during maintenance therapy with vincristine and prednisolone. The regimen produced remission in 96% of patients and molecular remission in 78%. On interim analysis, the 1-year DFS and OS were estimated at 68% and 89%, respectively. These estimates, although preliminary, appear superior to those in an earlier study without imatinib. [Towatari, 2004, preprint p2, 8, 9, 15, 16, 19, 28, 29]
Lee and colleagues administered imatinib at 600 mg/d during induction therapy with daunorubicin, vincristine, prednisolone, and L-aspariginase, and then at 400 mg/d during consolidation regimens to 20 newly diagnosed Ph+ ALL patients (median age, 37 years; range, years). The regimen produced remission in 95% of patients.Three-quarters of the cohort underwent allogeneic SCT in CR1. Median CR duration (2.2 years) and median survival (2.4 years) were more than twice those for an historical cohort of Ph+ ALL patients treated with the same chemotherapy regimen but without imatinib. [Lee, 2005, p1509, c1, ¶1; p1510, c1, ¶1]
Finally, Oriol and colleagues administered imatinib 400 mg/d during induction with vincristine, daunorubicin, and prednisolone and during consolidation therapy with mercaptopurine, high-dose methotrexate, VM-26, and cyclophosphamide to 30 patients with newly diagnosed Ph+ ALL (median age, 45 years; range, years).The CR rate of 90% was higher than the 70% rate seen in an earlier study conducted without imatinib. Median follow-up was too short to draw valid survival comparisons with the historical cohort. [Oriol, 2005, EHA abs]
Lee K-H, Lee J-H, Choi S-J, et al. Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Leukemia. 2005;19:
Oriol A, Ribera JM, Gonzalez M, et al. Treatment of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) with concurrent chemotherapy and imatinib mesylate [abstract]. Presented at: European Hematology Association. Stockholm, Sweden; Abstr
Towatari M, Yanada M, Usui N, et al. Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL positive acute lymphoblastic leukemia. Blood. 2004;104:

22. Event-free and Overall Survival of PH+ ALL
Comparison of ALL202 (+IM) and ALL93 (-IM)
EFS OS
(+IM)
(+IM)
57%
49%
(-IM)
(-IM)
Yanada et al. J Clin Oncol 2006

23. Survival of CR VHR < 55 y
GMALL 06/99 and 07/03
Survival of CR
VHR < 55 y
No IM: 0.14 (N=70
IM after Ind.2: 0.32 (N=37)
IM from Ind.2: 0.40 (N=74)
IM from Ind.1: 0.74 (N=36)

24. Imatinib in Adult Ph+ ALL (pts 15 – 55 y)
CONCLUSIONS
Increase in CR rate from 65-75% to 95%
Increase in Mol. CR rates from <5% to ~50%
Induction mortality low, but death in CR
Improvement in long-term outcome ?
Effect on SCT?

25. Treatment of Elderly
Ph+ ALL Patients

26. Imatinib Versus Chemotherapy Induction
GMALL Trial in Elderly de novo Ph+ ALL
N = 55; median age 68 years (58-79)
Randomized
induction
Consolidation
CR rate
Induction- 50%
Chemo-tx
Imatinib 96%
alone *
Imatinib C1 C2
Reind. C3 C4
[C5]*
Pre-
phase R
Imatinib
Chemo-
therapy       
weeks 1-4
1 year
* Imatinib Mono 400 mg/d for 4 weeks

27. Recent Approaches with Imatinib ± Chemo
in Elderly Patients with Ph+ ALL
Author Age Therapy IM
Year (Median) Induct Consol Dose N CR Survival
Vignetti y IM + Pred IM % % (1 yr)
Blood
2006
Delannoy y CTX IM + ster % (IM) % (1 yr)
Leukemia CTX / IM 70% (CH)
Ottmann y IM CTX+IM % (IM) % (1 yr)
Cancer CTX % (CH) % (2 yrs)
2007

28. Imatinib-Based Therapy in Elderly Ph(+) ALL: Comparison of Outcome
GMALL1
GIMEMA2
GRAALL3 %
EFS
DFS
DFS
AFR09
(+ IM)
hist. control
(no IM)
Days
Months
Months
1Ottman et al, Cancer 2007;109: ; 2 Vignetti et al. Blood. 2007;109(9):3676-8; 3Delannoy et al., Leukemia. 2006; 20:
High rate of mutations !

29. Monotherapy with Imatinib in Elderly Ph+ ALL
Conclusions
Increase of CR rate to >90%, no induction death
Molecular CR rate ~ 40 %
Improvement of median survival from 6 to 12 mo
Improvement of quality of life
- very low toxicity and
- partly outpatient treatment
Outcome impaired due to development of resistance

30. BCR-ABL Mutations
in Ph+ ALL
(GMALL - Elderly)

31. Mechanism of Resistance in Ph+ ALL Hofmann et al, Blood & Lancet 2002
Single point mutation in ATP binding site (e.g. T315I), P-loop or activation loop
Amplification of bcr-abl fusion gene
Up-regulation of bcr-abl transcription
Increase of imatinib efflux / decreased cellular bioavailability
BCR-ABL independence (SRC)

32. Proportion of Mutant BCR-ABL Alleles in Relation
to Treatment Response of de novo Ph+ALL
% unmutated
BCR-ABL
% mutated
BCR-ABL
REL CR
CRmol
Time
Chemotherapy
IMATINIB
H.Pfeifer,O.G.Ottmann

33. Novel Bcr-Abl inhibitors
AMN107 Novartis
Dasatinib BMS
VX-680 (L-00128) MSD (T315i)
Aurorakinase-Inh.
SGX70393 Novartis (T315i)
LBH589 Novartis
HDAC-Inhibitor

34. Experience with Dasatinib in front-line Therapy of Ph+ ALL
Author N Age Dose CR MolCR
Chemo
Ravandi mg bid 93% 46%
ASH 2007, #2814 (23-79) HyperCVAD
Foa mg bid 100% 70%
ASH 2007, #7 (30-74) Pred <10-2
 Tolerable in combination with chemo
 Effectivity comparable to Imatinib
 Long-term results pending

35. New Drugs in ALL Explored in GMALL studies Nelarabine Cytostatics
Clofarabine
Forodesine HCL
Banoxantrone
Liposomal ARAC for i.th. use
Liposomal VCR
Liposomal DNR
Anti CD20
AntiCD52
AntiCD33
AntiCD19 / Tcell engager
Imatinib
Nilotinib
Dasatinib
Aurorakinase Inhibitors + others
Liposomal
Antibodies
Kinase inhibitors

36. Antigen Surface Expression in Subtypes of Adult ALL and Monoclonal Antibodies
Surface Subtype Expression on Antibody Evidence
antigen >20% LBC* in ALL
CD20 B-precursor % Rituximab Trials de novo
Mature B-ALL % ALL
CD52 B-/T-lineage % / 77% Alemtuzumab Trials de novo
ALL
CD33 B-/T-lineage % / 9% Gemtuzumab Case reports
Ph+ ALL %
CD B-precursor %
Mature B-ALL %
CD22 B-lineage % Epratuzumab
*E.Thiel, S.Schwartz, W.D.Ludwig; Central immunophenotyping for GMALL studies

37. Rituximab in Different Subentities of Adult ALL
Mature B-ALL / Burkitt‘s NHL
B-precursor ALL
- Elderly
- Younger
- standard risk
- high risk
Relapsed ALL
Therefore mature B-ALL and Burkitt‘s NHL was the first entity in which the GMALL study group tested Rituximab therapy.

38. Treatment Results in Burkitt‘s Lymphoma/Leukemia
With Short Intensive Therapies  
Weighted mean 80% 59%
CR rate 80%; Survival 59%
Results depend on proportion of B-ALL
Survival around 70% in Burkitt‘s NHL

39. GMALL B-ALL/NHL 2002 Trial

40. Rationale for B-ALL/NHL Study 2002
Anti CD20 (Rituximab)
Results from NHL protocols with Rituximab
Expression of CD20 >80% in mature B-ALL
HDMTX
Dose reduction from 3 g/m² to 1.5 g/m² since no improvement but more toxicity in B-NHL90
HDAC
To improve antileukemic activity and CNS prophylaxis
Favourable results from other studies e.g. HyperCVAD
G-CSF
Lower incidence of severe neutropenia and mucositis
Salvage therapies
As prophylaxis (CNS, MedTU,extranodal inv.) and salvage therapy
SC apheresis in HR pts for potential auto SCT

41. SC- Apheresis (not obligatory)
Multicentre Study to Optimize Therapy of B-ALL and High-grade Non-Hodgkin’s Lymphoma in Adults (GMALL-B-ALL/NHL 2002)
Patients years
Failure of therapy
Salvage
SCT (allo, auto, MUD) P A1 B1 C1 A2 B2 C2
antiCD20 1
antiCD20
antiCD20
antiCD20
antiCD20
antiCD20
antiCD20
antiCD20
SC- Apheresis (not obligatory)
End of therapy in
Stage I/II with
CR after 2 cycles
MedTU
CNS-inv.
CRu, PR
Irradiation
Patients > 55 yrs P
A1 *
B1 *
A2 *
B2 *
A3 *
B3 *
antiCD20 1
antiCD20
antiCD20
antiCD20
antiCD20
antiCD20
antiCD20
antiCD20 1 2 5 8 12 15 18 21 24 28
Weeks
Failure of therapy
Salvage
SCT (allo, auto, MUD)
End of therapy after 4 cycles in Stage I/II with CR after 2 cycles

42. GMALL Study for Adult B-ALL and High Grade B-NHL
(GMALL B-ALL/NHL 2002)
Pre-phase
CYCLO 200 mg/m² d 1-5
PRED 60 mg/m² d 1-5 1 2 3 4
5 days
Block A
Anti-CD mg/m² d 0
DEXA 10 mg/m² d 1-5
VCR 2 mg (abs) d 1
HD-MTX 1.5 g/m² * d 1
IFO 800 mg/m² d 1-5
ARAC 150 mg/m²x2 d 4,5
VM mg/m² d 4,5
DEXA/ARAC/MTX i.th. d 1,5
G-CSF d 7 1 2 3 4 5 6
7 days
* 0.5 g/m² if > 55y

43. GMALL Study for Adult B-ALL and High Grade B-NHL
(GMALL B-ALL/NHL 2002)
Block B
Anti-CD mg/m² d 0
DEXA 10 mg/m² d 1-5
VCR 2 mg (abs) d 1
HD-MTX 1.5 g/m² * d 1
CP 200 mg/m² d 1-5
ADR 25 mg/m²x2 d 4,5
DEXA/ARAC/MTX i.th. d 1,5
G-CSF d 7 1 2 3 4 5 6
7 days
* 0.5 g/m² if > 50y
Block C
Anti-CD mg/m² d 0
DEXA 10 mg/m² d 1-5
VDS 3 mg/m² d 1
HD-MTX 1.5 g/m² * d 1
VP mg/m² d 4,5
HD-AC 2 g/m² x 2** d 5
DEXA/ARAC/MTX i.th. d 1,5
G-CSF d 7 1 2 3 4 5 6
7 days
* g/m² if > 55y
** 1 g/m² if > 55 y

44. GMALL B-ALL/NHL 2002 Evaluable Patients
Accrual period: 9/ /2007
N evaluable: 381 (minimum 2 cycles completed)
Diagnoses: B-ALL (22%)
Burkitt (38%) 32 atyp./B-like
DLBCL (27%) 70 mediastinal
B-LBL (6%)
LCAL (7%)

45. Results of Remission Evaluation
GMALL B-ALL/NHL 2002
Response CR PR
Failure
Death under therapy
Burkitt/Burkitt like
N=129
118(91%)
3(2%)
5(4%)
B-ALL
N=77
65(84%)
3(4%)
2(3%)
7(9%)
DLBCL
N=94
71(76%)
13(14%)
5(5%)

46. Overall Survival (<55 yrs)
GMALL B-ALL/NHL 2002
Burkitt 0.93 (N=101)
B-ALL 0.76 (N=49)
DLBCL (N=74)
Majority of events < 1 y

47. Overall Survival Burkitt / Burkitt‘s-like Lymphoma
GMALL B-ALL/NHL 2002
Burkitt 0.93 (N=101)
Burkitt-like 0.91 (N=28)

48. Rituximab in Combination with Hyper-CVAD in Mature B-ALL/Burkitt‘s NHL
Thomas et al , Cancer 2006
Hyper-
CVAD
HDMTX
ARAC
Hyper-
CVAD
HDMTX
ARAC
Hyper-
CVAD
HDMTX
ARAC
Hyper-
CVAD
HDMTX
ARAC
Rituximab 375 mg/m² 2 4 6 8 10 12 14 16 18 20 22 24 26
weeks
Hyper-CVAD+R Hyper-CVAD
Evaluable 31 (14 B-ALL) 48
CR 86% 85%
OS (3y) 89% 53%
> 60 89% 19%
Relapses 7% 34%
> 60 yrs 0% 50%
Toxicity ± R comparable

49. Burkitt‘s NHL in HIV+ pts

50. Short Intensive Chemotherapy in HIV+ Adult Burkitt‘s NHL
Author Year Age Stage III/IV L3-ALL HAART Protocol N CR OS
Horst et al n.r. 70%* 8%* 60% GMALL B-ALL 16 87% 72%
0.5-3 g/m² MTX
Wang et al (19-61)* 88% 29%* n.r. CODOX-M 8 63% 60%
7 g/m² MTX
Astrow et al (27-59) 83% 76% n.r. McMasters 23 39% 39%
200 mg/m²
Oriol et al (23-65) 57% 43% 36% GMALL B-ALL 14 71% 55%
3 g/m² MTX
Costello et al % n.r. n.r. CHOP augm. 13 n.r. 60%
8 g/m² MTX
Cortes et al (32-55) 29% 50% 64% HyperCVAD 14 92% 48%
1 g/m² MTX
Weighted mean % 54%
* Whole cohort including arm with less intensive chemotherapy

51. Overall Survival in Adult B-ALL/B-NHL
GMALL B-ALL/NHL 2002
B-ALL/NHL 2002: 0.80 (N=272)
B-ALL/NHL 90: 0.54 (N=270)
p=0.0001

52. Mature B-ALL/Burkitt‘s NHL Summary and Conclusions
Combination of Rituximab and intensive chemo feasible
Response rate % in Burkitt / DLBCL, overall survival ~ 90%
Improvement in mature B-ALL, less for pts > 55 y
Irradiation of residual tumors effective salvage therapy
SCT: No prognostic factors  no indication for SCT in CR1  No stem cell apheresis any more
Major toxicity: mucositis

53. Mature B-ALL/Burkitt‘s NHL
Future Prospects - I
Reduction of toxicity
De-escalation in good responders and early stages ? e.g.
- Reduced MTX infusion time?
- Reduction of cycles?
Improved prophylaxis of mucositis and infections
Improvment of outcome in elderly B-ALL
Intensified CNS prophylaxis e.g. Depocyte
HDAC based cycle
Increased Rituximab dose-intensity ?
Refinition of response evaluation and risk stratification e.g.
PET analysis
MRD analysis (Mussolin et al, JCO 2007)

54. GMALL- Study Group + ~126 participating centers
Study Center Head D.Hoelzer, Frankfurt
Coordinator N.Gökbuget, Frankfurt
Data Manager R.Reutzel, Frankfurt
Central Diagnosis Morphology/Cytochemisty H.Horst, Kiel
Immunphenotyping E.Thiel, S.Schwartz,
Molecular genetics T.Burmeister, Berlin
Gene expression analysis W.K.Hofmann, Berlin
Cytogenetics H.Rieder, Düsseldorf
C.Schoch, München
Minimal M.Kneba, M.Brüggemann,T. Raff, Kiel
Residual Disease H. Pfeifer, Frankfurt
Molecular therapies O. Ottmann, Frankfurt
SCT coordinator R.Arnold, Berlin
Irradiation therapy R.Fietkau, Rostock
Statistics GMALL Study Center
+ ~126 participating centers