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1 Supplementary webappendix This webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Elter T, Gercheva-Kyuchukova L, Pylylpenko H, et al. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial. Lancet Oncol 2011; published online Oct 11, DOI: /S (11)70242-X.

2 Web Extra Table 1: AEs Occurring in 5% of Rai Stage I-II Patients (N=102) (N=102) Rai stage I-II patients with at least 1 AE 101 (99 0) (86 3) Pyrexia 64 (62 7) (1 9) Neutropenia 53 (52 0) (47 1) Leukopenia 48 (47 1) (17 6) Chills 33 (32 4) (1 0) Thrombocytopenia 27 (26 5) (20 6) Lymphopenia 24 (23 5) (3 9) Anaemia 23 (22 3) (16 7) Urticaria 16 (15 7) (1 0) CMV test positive 16 (15 7) (1 0) Rash 16 (15 7) (3 9) Infusion-related reaction 15 (14 7) (0 0) Dermatitis allergic 10 (9 8) (2 9) Bronchitis 10 (9 8) (2 9) Cough 10 (9 8) (2 9) Hypertension 10 (9 8) (3 9) Nausea 9 (8 8) (9 8) Diarrhoea 8 (7 8) (4 9) Bronchospasm 8 (7 8) (0 0) Pruritus 7 (6 9) (2 0) Increased ALT 6 (5 9) (3 9) Bone pain 6 (5 9) (0 0) Headache 6 (5 9) (3 9) Pharyngitis 6 (5 9) (2 0) Vomiting 6 (5 9) (2 0) Fatigue 4 (3 9) (5 9) AE, adverse event (regardless of causality, unless otherwise specified); CMV, Cytomegalovirus; ALT, Alanine transaminase Page 1 of 6 Web Extra Material

3 Web Extra Table 2: AEs Occurring in 5% of Rai Stage III-IV Patients (N=60) (N=61) Any grade Maximum Grade Any grade Maximum Grade Rai stage III-IV patients with at least 1 AE 58 (96 7) (96 7) Pyrexia 33 (55 0) (19 7) Neutropenia 32 (53 3) (55 7) Leukopenia 25 (41 7) (11 5) Thrombocytopenia 20 (33 3) (39 3) Chills 16 (26 7) (1 6) Anaemia 12 (20 0) (37 7) Nausea 11 (18 3) (4 9) Lymphopenia 11 (18 3) (4 9) Rash 9 (15 0) (1 6) Vomiting 9 (15 0) (1 6) Headache 8 (13 3) (0 0) Diarrhoea 8 (13 3) (9 8) Infusion-related reaction 8 (13 3) (0 0) Fatigue 7 (11 7) (4 9) Pruritus 7 (11 7) (3 3) Urticaria 7 (11 7) (4 9) Bronchitis 6 (10 0) (3 3) Decreased WBC count 6 (10 0) (3 3) Cytokine release syndrome 5 (8 3) (0 0) Constipation 5 (8 3) (0 0) Insomnia 5 (8 3) (0 0) Pneumonia 5 (8 3) (4 9) Dermatitis allergic 4 (6 7) (0 0) Dyspnoea 4 (6 7) (0 0) Decreased neutrophil count 4 (6 7) (9 8) Decreased platelet count 4 (6 7) (13 1) Bone pain 3 (5 0) (0 0) Cough 3 (5 0) (8 2) CMV test positive 3 (5 0) (0 0) Dizziness 3 (5 0) (3 3) Decreased haemoglobin 3 (5 0) (8 2) Hiccups 3 (5 0) (0 0) Respiratory tract infection 3 (5 0) (4 9) Pollakiuria 3 (5 0) (0 0) Febrile Neutropenia 1 (1 7) (9 8) AE, adverse event (regardless of causality, unless otherwise specified); CMV, Cytomegalovirus; WBC, White blood cell Page 2 of 6 Web Extra Material

4 Web Extra Table 3: AEs Occurring in 5% of Patients 65 years of Age (N=55) (N=59) Patients 65 years old with at least 1 AE 54 (98 2) (94 9) Pyrexia 30 (54 5) (5 1) Neutropenia 28 (50 9) (54 2) Leukopenia 22 (40 0) (22 0) Chills 20 (36 4) (3 4) Thrombocytopenia 17 (30 9) (30 5) Lymphopenia 13 (23 6) (5 1) Anaemia 12 (21 8) (30 5) Diarrhoea 8 (14 5) (6 8) Rash 8 (14 5) (1 7) Cough 7 (12 7) (6 8) Hypertension 7 (12 7) (8 5) Nausea 7 (12 7) (5 1) CMV test positive 6 (10 9) (1 7) Pruritus 6 (10 9) (1 7) Vomiting 6 (10 9) (0 0) Infusion-related reaction 5 (9 1) (0 0) Pneumonia 5 (9 1) (3 4) Urticaria 5 (9 1) (3 4) Increased blood creatinine 4 (7 3) (1 7) Bone pain 4 (7 3) (0 0) Decreased WBC count 4 (7 3) (3 4) Back pain 3 (5 5) (1 7) Bronchitis 3 (5 5) (1 7) Constipation 3 (5 5) (3 4) Dizziness 3 (5 5) (3 4) Dyspnoea 3 (5 5) (0 0) Fatigue 3 (5 5) (6 8) Febrile neutropenia 3 (5 5) (6 8) Headache 3 (5 5) (0 0) Nasopharyngitis 3 (5 5) (8 5) Decreased neutrophil count 3 (5 5) (6 8) Decreased platelet count 3 (5 5) (10 2) Pleural effusion 3 (5 5) (0 0) Urinary tract infection 3 (5 5) (0 0) Increased ALT 2 (3 6) (5 1) Asthenia 2 (3 6) (8 5) Decreased haemoglobin 2 (3 6) (5 1) Abdominal pain upper 0 (0 0) (5 1) Upper respiratory tract infection 0 (0 0) (5 1) AE, adverse event (regardless of causality, unless otherwise specified); CMV, Cytomegalovirus; WBC, White blood cell count; ALT, Alanine transaminase Page 3 of 6 Web Extra Material

5 Web Extra Table 4: AEs Occurring in 5% of Patients < 65 years of Age (N=109) (N=106) Patients 65 years old with at least 1 AE 107 (98 2) (87 7) Pyrexia 68 (62 4) (11 3) Neutropenia 58 (53 2) (49 1) Leukopenia 52 (47 7) (12 3) Thrombocytopenia 30 (27 5) (25 5) Chills 29 (26 6) (0 0) Anaemia 24 (22 0) (21 7) Lymphopenia 22 (20 2) (3 8) Infusion-related reaction 18 (16 5) (0 0) Urticaria 18 (16 5) (1 9) Rash 17 (15 6) (3 8) CMV test positive 14 (12 8) (0 0) Bronchitis 13 (11 9) (3 8) Nausea 13 (11 9) (9 4) Dermatitis allergic 12 (11 0) (3 8) Headache 11 (10 1) (3 8) Vomiting 9 (8 3) (2 8) Diarrhoea 8 (7 3) (6 6) Fatigue 8 (7 3) (4 7) Pruritus 8 (7 3) (2 8) Bronchospasm 7 (6 4) (0 0) Cough 6 (5 5) (3 8) Cytokine release syndrome 6 (5 5) (0 0) Hyperthermia 6 (5 5) (0 0) Pharyngitis 6 (5 5) (4 7) Pneumonia 6 (5 5) (0 9) AE, adverse event (regardless of causality, unless otherwise specified); CMV, Cytomegalovirus Page 4 of 6 Web Extra Material

6 Web Extra Table 5: AEs Occurring in 5% of Male Patients (N=105) (N=106) Male patients with at least 1 AE 103 (98 1) (89 6) Pyrexia 61 (58 1) (8 5) Neutropenia 51 (48 6) (46 2) Leukopenia 40 (38 1) (14 2) Thrombocytopenia 32 (30 5) (27 4) Chills 30 (28 6) (1 9) Anaemia 15 (14 3) (22 6) Lymphopenia 14 (13 3) (2 8) Rash 12 (11 4) (2 8) Urticaria 12 (11 4) (1 9) Bronchitis 11 (10 5) (1 9) Infusion-related reaction 11 (10 5) (0 0) Nausea 10 (9 5) (7 5) CMV DNA test positive 9 (8 6) (0 9) Diarrhoea 9 (8 6) (3 8) Fatigue 9 (8 6) (5 7) Vomiting 8 (7 6) (1 9) Cough 7 (6 7) (4 7) Headache 7 (6 7) (1 9) Dermatitis allergic 6 (5 7) (0 9) Hypertension 6 (5 7) (4 7) Pneumonia 6 (5 7) (1 9) Decreased platelet count 3 (2 9) (5 7) AE, adverse event (regardless of causality, unless otherwise specified); CMV, Cytomegalovirus Page 5 of 6 Web Extra Material

7 Web Extra Table 6: AEs Occurring in 5% of Female Patients (N=59) (N=59) Female patients with at least 1 AE 58 (98 3) (91 5) Pyrexia 37 (62 7) (10 2) Neutropenia 35 (59 3) (59 3) Leukopenia 34 (57 6) (18 6) Anaemia 21 (35 6) (28 8) Lymphopenia 21 (35 6) (6 8) Chills 19 (32 2) (0 0) Thrombocytopenia 15 (25 4) (27 1) Rash 13 (22 0) (3 4) Infusion-related reaction 12 (20 3) (0 0) Urticaria 11 (18 6) (3 4) CMV test positive 11 (18 6) (0 0) Nausea 10 (16 9) (8 5) Pruritus 9 (15 3) (3 4) Dermatitis allergic 8 (13 6) (5 1) Bronchospasm 7 (11 9) (0 0) Diarrhoea 7 (11 9) (11 9) Headache 7 (11 9) (3 4) Vomiting 7 (11 9) (1 7) Bone pain 6 (10 2) (0 0) Cough 6 (10 2) (5 1) Hypertension 6 (10 2) (1 7) Bronchitis 5 (8 5) (5 1) Pneumonia 5 (8 5) (1 7) Cholecystitis chronic 4 (6 8) (1 7) Drug eruption 4 (6 8) (0 0) Stomatitis 4 (6 8) (0 0) Asthenia 3 (5 1) (3 4) CMV infection 3 (5 1) (0 0) Decreased haemoglobin 3 (5 1) (5 1) Decreased platelet count 3 (5 1) (6 8) Pollakiuria 3 (5 1) (0 0) Pruritus allergic 3 (5 1) (0 0) Respiratory tract infection viral 3 (5 1) (1 7) Decreased WBC count 3 (5 1) (3 4) Fatigue 2 (3 4) (5 1) Nasopharyngitis 2 (3 4) (6 8) Decreased neutrophil count 2 (3 4) (5 1) Febrile neutropenia 2 (3 4) (6 8) Respiratory tract infection 1 (1 7) (5 1) Herpes zoster 0 (0 0) (5 1) Peripheral sensory neuropathy 0 (0 0) (5 1) AE, adverse event (regardless of causality, unless otherwise specified); CMV, Cytomegalovirus; WBC, White blood cell Page 6 of 6 Web Extra Material

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