On Location 2015 ASH Annual Meeting
Long Live the Platelets:
Does Extended Platelet Survival Affect Outcomes?
Inhibiting normal apoptosis leads to extended platelet survival, but these
longer-living or “exhausted” platelets may have compromised hemostatic
efficacy, according to research presented by Irina Pleines, PhD, at the
2015 ASH Annual Meeting. The results demonstrate that efforts to extend platelet survival times in blood bank storage serve no real purpose.
Platelet lifespan is limited to 10 days in humans and five days in mice
and is regulated by the intrinsic apoptosis pathway, in which the prosurvival protein Bcl-xL restrains the essential death mediators Bak and
Bax. “Hence, platelet lifespan and platelet counts in mice are increased
in the absence of Bak and Bak/Bax,” Dr. Pleines, from the Walter & Eliza
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without a dose reduction, 50% in the REVLIMID/dexamethasone
treatment group had at least one additional dose interruption with or
without a dose reduction compared to 21% in the placebo/dexamethasone
treatment group. Most adverse reactions and Grade 3/4 adverse reactions
were more frequent in patients who received the combination of
REVLIMID/dexamethasone compared to placebo/dexamethasone.
Table 5: Adverse Reactions Reported in ≥5% of Patients and with a
≥2% Difference in Proportion of Patients Between the
REVLIMID/dexamethasone and Placebo/dexamethasone Groups
System Organ Class/ Preferred Term REVLIMID/Dex* Placebo/Dex *
(N=353)
(N=350)
n (%)
n (%)
Tables 5, 6, and 7 summarize the adverse reactions reported for
REVLIMID/dexamethasone and placebo/dexamethasone groups.
Metabolism and nutrition disorders
Anorexia
Hypokalemia
Hypocalcemia
Appetite Decreased
Dehydration
Hypomagnesemia
Investigations
Weight Decreased
Eye disorders
Blurred vision
Vascular disorders
Deep vein thrombosis%
Hypertension
Hypotension
55 (15.6)
48 (13.6)
31 (8.8)
24 (6.8)
23 (6.5)
24 (6.8)
34 (9.7)
21 (6.0)
10 (2.9)
14 (4.0)
15 (4.3)
10 (2.9)
69 (19.5)
52 (14.9)
61 (17.3)
40 (11.4)
33 (9.3)
28 (7.9)
25 (7.1)
15 (4.3)
20 (5.7)
15 (4.3)
Table 6: Grade 3/4 Adverse Reactions Reported in ≥2% Patients
and With a ≥1% Difference in Proportion of Patients Between the
REVLIMID/dexamethasone and Placebo/dexamethasone groups
System Organ Class/ Preferred Term REVLIMID/Dex# Placebo/Dex#
(N=353)
(N=350)
n (%)
n (%)
Blood and lymphatic system disorders
Neutropenia%
118 (33.4)
12 (3.4)
Thrombocytopenia@
43 (12.2)
22 (6.3)
Anemia@
35 (9.9)
20 (5.7)
Leukopenia
14 (4.0)
1 (0.3)
Lymphopenia
10 (2.8)
4 (1.1)
Febrile Neutropenia%
8 (2.3)
0 (0.0)
General disorders and administration site conditions
Fatigue
23 (6.5)
17 (4.9)
Vascular disorders
Deep vein thrombosis%
29 (8.2)
12 (3.4)
Infections and infestations
Pneumonia@
30 (8.5)
19 (5.4)
Urinary Tract Infection
5 (1.4)
1 (0.3)
Metabolism and nutrition disorders
Hypokalemia
17 (4.8)
5 (1.4)
Hypocalcemia
13 (3.7)
6 (1.7)
Hypophosphatemia
9 (2.5)
0 (0.0)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism@
14 (4.0)
3 (0.9)
Respiratory Distress@
4 (1.1)
0 (0.0)
Musculoskeletal and connective tissue disorders
Muscle weakness
20 (5.7)
10 (2.9)
Gastrointestinal disorders
Diarrhea@
11 (3.1)
4 (1.1)
Constipation
7 (2.0)
1 (0.3)
Nausea@
6 (1.7)
2 (0.6)
Cardiac disorders
Atrial fibrillation@
13 (3.7)
4 (1.1)
Tachycardia
6 (1.7)
1 (0.3)
Cardiac Failure Congestive@
5 (1.4)
1 (0.3)
Nervous System disorders
Syncope
10 (2.8)
3 (0.9)
Dizziness
7 (2.0)
3 (0.9)
(continued)
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Table 5: Adverse Reactions Reported in ≥5% of Patients and with a
≥2% Difference in Proportion of Patients Between the
REVLIMID/dexamethasone and Placebo/dexamethasone Groups
System Organ Class/ Preferred Term REVLIMID/Dex* Placebo/Dex *
(N=353)
(N=350)
n (%)
n (%)
Blood and lymphatic system disorders
Neutropenia %
149 (42.2)
22 (6.3)
Anemia@
111 (31.4)
83 (23.7)
Thrombocytopenia@
76 (21.5)
37 (10.6)
Leukopenia
28 (7.9)
4 (1.1)
Lymphopenia
19 (5.4)
5 (1.4)
General disorders and administration site conditions
Fatigue
155 (43.9)
146 (41.7)
Pyrexia
97 (27.5)
82 (23.4)
Peripheral edema
93 (26.3)
74 (21.1)
Chest Pain
29 ( 8.2)
20 (5.7)
Lethargy
24 ( 6.8)
8 (2.3)
Gastrointestinal disorders
Constipation
143 (40.5)
74 (21.1)
Diarrhea@
136 (38.5)
96 (27.4)
Nausea@
92 (26.1)
75 (21.4)
Vomiting@
43 (12.2)
33 (9.4)
Abdominal Pain@
35 (9.9)
22 (6.3)
Dry Mouth
25 (7.1)
13 (3.7)
Musculoskeletal and connective tissue disorders
Muscle cramp
118 (33.4)
74 (21.1)
Back pain
91 (25.8)
65 (18.6)
Bone Pain
48 (13.6)
39 (11.1)
Pain in Limb
42 (11.9)
32 (9.1)
Nervous system disorders
Dizziness
82 (23.2)
59 (16.9)
Tremor
75 (21.2)
26 (7.4)
Dysgeusia
54 (15.3)
34 (9.7)
Hypoaesthesia
36 (10.2)
25 (7.1)
Neuropathyª
23 (6.5)
13 (3.7)
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea
83 (23.5)
60 (17.1)
Nasopharyngitis
62 (17.6)
31 (8.9)
Pharyngitis
48 (13.6)
33 (9.4)
Bronchitis
40 (11.3)
30 (8.6)
Infectionsb and infestations
Upper respiratory tract infection
87 (24.6)
55 (15.7)
Pneumonia@
48 (13.6)
29 (8.3)
Urinary Tract Infection
30 (8.5)
19 (5.4)
Sinusitis
26 (7.4)
16 (4.6)
Skin and subcutaneous system disorders
Rashc
75 (21.2)
33 (9.4)
Sweating Increased
35 (9.9)
25 (7.1)
Dry Sk in
33 (9.3)
14 (4.0)
Pruritus
27 (7.6)
18 (5.1)
(continued)