Approaches to management of β-thalassemia intermedia Ali Taher, MD, PhD, FRCP American University...

Approaches to management of β-thalassemia intermedia

Ali Taher, MD, PhD, FRCPAmerican University of Beirut Medical Center

Agenda

● Overview of β-thalassemia intermedia (TI)

● Overview of TI complications

● Management of TI● Splenectomy

● Transfusion

● Iron chelation therapy

● Hydroxycarbamide

● Other treatments

● Take home message

Introduction

β-thalassemia Minor

β-thalassemia Intermedia

β-thalassemia Major

Mild asymptomatic anemia

Severe transfusion-dependent anemia

Intermediate phenotype with variable clinical severity

Musallam KM, et al. Cold Spring Harb Perspect Med. 2012; 2:a013482

It was previously thought that TI patients do not require treatment since their symptoms are mild

Because thalassemia intermedia has such a variable phenotype, therapy must be tailored for each patient.

Pathophysiology

● The clinical sequelae of β-TI are due to three main persistent factors:

● Mildly affected patients may be asymptomatic until adult life● Severely affected patients generally present between 2–6 years of age

Ineffective erythropoiesis

Massive erythroid marrow hypertrophy

Chronic anemia

Gastrointestinal iron absorption

Iron overload

Ineffective erythropoiesis

Peripheral breakdown of red blood cells

Gastrointestinal iron absorption

Musallam KM, et al. Cold Spring Harb Perspect Med. 2012; 2:a013482

First attempt at understandingcomplications in TI vs TM

Complication (% of patients affected)

TI TM

Lebanon Italy Lebanon Italy

(n = 37) (n = 63) (n = 40) (n = 60)

Splenectomy 90 67 95 83

Cholecystectomy 85 68 15 7

Gallstones 55 63 10 23

Extramedullary hemopoiesis 20 24 0 0

Leg ulcers 20 33 0 0

Thrombotic events 28 22 0 0

Cardiopathy* 3 5 10 25

Pulmonary hypertension† 50 17 10 11

Abnormal liver enzymes 20 22 55 68

HCV infection 7 33 7 98

Hypogonadism 5 3 80 93

Diabetes mellitus 3 2 12.5 10

Hypothyroidism 3 2 15 11

Taher A, Isma’eel H, Cappellini MD. Blood Cells Mol Dis. 2006;37:12-20.HCV = hepatitis C virus.

*Fractional shortening < 35%. †Defined as pulmonary artery systolic pressure > 30 mmHg; a well-enveloped tricuspid regurgitant jet velocity could be detected in only 20 patients, so frequency was assessed in these patients only.

Overview on Practices in Thalassemia Intermedia Management Aiming for Lowering Complication-rates Across a Region of Endemicity: the OPTIMAL CARE study

● Cross-sectional study of 584 TI patients from 6 comprehensive care centers in the Middle East and Italy

Taher AT, Musallam KM, Karimi M, et al. Blood. 2010;115:1886-92.

N = 12S Daar

N = 127AT Taher

KM Musallam

N = 51A El-Beshlawy

N = 153MD Cappellini

N = 200M Karimi

N = 41K BelhoulM Saned

http://upload.wikimedia.org/wikipedia/commons/0/03/Flag_of_Italy.svg

The OPTIMAL CARE study: overall study population

ParameterFrequency

n (%)

Age (years)< 18 172 (29.5 )18–35 288 (49.3) > 35 124 (21.2)

Male:female 291 (49.8) : 293 (50.2)Splenectomized 325 (55.7)Serum ferritin (µg/L)

< 1,000 376 (64.4)1,000–2,500 179 (30.6)> 2,500 29 (5)

Complications

OsteoporosisEMHHypogonadism CholelithiasisThrombosis Pulmonary hypertensionAbnormal liver functionLeg ulcers HypothyroidismHeart failureDiabetes mellitus

134 (22.9)124 (21.2)101 (17.3)100 (17.1)

82 (14)64 (11)57 (9.8)46 (7.9)33 (5.7)25 (4.3)10 (1.7)

TreatmentFrequency

n (%)Hydroxyurea 202 (34.6)Transfusion

NeverOccasionalRegular

139 (23.8)143 (24.5)302 (51.7)

Iron chelationNoneDeferoxamineDeferiproneDeferiprone + deferoxamineDeferasirox

248 (42.5)300 (51.4)

12 (2.1)3 (0.5)

21 (3.6)

EMH = extramedullary hematopoiesis. Taher AT, Musallam KM, Karimi M, et al. Blood. 2010;115:1886-92.

Complications of β-TI

● Hypercoagulability and thrombosis

● Brain abnormalities

● Pulmonary hypertension

● Leg ulcers

● Extramedullary hematopoiesis

● Hepatocellular carcinoma

● Renal abnormalities

● Iron overload

● ……….…4

TI complications increase with age

Taher AT et al. Br J Haematol 2010;150:486–489

0

EMH

Fre

quen

cy (

%)

< 10 years 11–20 years 21–32 years >32 years

5

10

15

20

25

30

35

40

45

Leg

ulcer

s

Throm

bosis PHT HF

Cholel

ithias

isALF DM

Hypot

hyro

idism

Osteop

oros

is

Hypog

onad

ism

6.7

13.3

16.7

40.0

26.7

3.3

6.7

16.7

26.7

3.3

13.3

20.0 20.0

3.3

6.7

10.0 10.0

0

3.3

6.7

33.3

13.3

10.0

20.0

13.3

3.3

6.7

10.0

13.3

0 0

3.3

16.7

0

3.3

10.0

30.0

6.7

16.7

23.3

20.0

0

16.7

23.3

EMH, extramedullary hematopoiesis; PHT, pulmonary hypertension; HF, heart failure; ALF, abnormal liver function; DM, diabetes mellitus

*statistically significant trend; † no splenectomy, HU, transfusion or chelation

*

* *

**

*

120 TI, treatment-naïve† patients from Lebanon, Italy, Iran, Egypt, UAE

and Oman

Transfusion therapy

Musallam KM, et al. Cold Spring Harb Perspect Med. 2012; 2:a013482.Taher AT, et al. Br J Haematol. 2011;152:512–23.

Complication Parameter RR 95% CI p value

EMH Splenectomy 0.44 0.26–0.73 0.001Transfusion 0.06 0.03–0.09 < 0.001Hydroxyurea 0.52 0.30–0.91 0.022

Pulmonary hypertension Age > 35 years 2.59 1.08–6.19 0.032Splenectomy 4.11 1.99–8.47 < 0.001Transfusion 0.33 0.18–0.58 < 0.001Hydroxyurea 0.42 0.20–0.90 0.025Iron chelation 0.53 0.29–0.95 0.032

Heart failure Transfusion 0.06 0.02–0.17 < 0.001Thrombosis Age > 35 years 2.60 1.39–4.87 0.003

Hb ≥ 9 g/dL 0.41 0.23–0.71 0.001Serum ferritin ≥ 1,000 µg/L 1.86 1.09–3.16 0.023Splenectomy 6.59 3.09–14.05 < 0.001Transfusion 0.28 0.16–0.48 < 0.001

Cholelithiasis Age > 35 years 2.76 1.56–4.87 < 0.001Female 1.96 1.18–3.25 0.010Splenectomy 5.19 2.72–9.90 < 0.001Transfusion 0.36 0.21–0.62 < 0.001Iron chelation 0.30 0.18–0.51 < 0.001

Abnormal liver function Serum ferritin ≥ 1,000 µg/L 1.74 1.00–3.02 0.049

The OPTIMAL CARE studyOccasionally/regularly transfused patients: 445/584



Leg ulcers Age > 35 years 2.09 1.05–4.16 0.036Splenectomy 3.98 1.68–9.39 0.002Transfusion 0.39 0.20–0.76 0.006Hydroxyurea 0.10 0.02–0.43 0.002

Hypothyroidism Splenectomy 6.04 2.03–17.92 0.001Hydroxyurea 0.05 0.01–0.45 0.003

Osteoporosis Age > 35 years 3.51 2.06–5.99 < 0.001Female 1.97 1.19–3.27 0.009Splenectomy 4.73 2.72–8.24 < 0.001Transfusion 3.10 1.64–5.85 < 0.001Hydroxyurea 0.02 0.01–0.09 < 0.001Iron chelation 0.40 0.24–0.68 0.001

Hypogonadism Female 2.98 1.79–4.96 < 0.001Serum ferritin ≥ 1,000 µg/L 2.63 1.59–4.36 < 0.001Transfusion 16.13 4.85–52.63 < 0.001Hydroxyurea 4.32 2.49–7.49 < 0.001Iron chelation 2.51 1.48–4.26 0.001

The OPTIMAL CARE studyOccasionally/regularly transfused patients: 445/584


Transfusion therapy was protective for thrombosis, EMH, PHT, HF, cholelithiasis, and leg ulcers

Transfusion therapy was associated with an increased risk of endocrinopathy

Transfusion

●Risk factors for alloimmunization :● Minimally transfused and newly transfused patients

● Old age at first transfusion

● Ethnic and racial diverse population

● Splenectomy

● Allogeneic WBC within the transfusate

• Management:• Fully phenotyped matched blood should be given• Erythropoietin in combination with iron and folic acid

Chou ST et al. Br J Haematol. 2012. [Epub ahead of print]

LIC Risk thresholds for development of complications in TI patients

1. Taher A, et al. Am J Hematol. 2010;85:288-90. 2. Origa R, et al. Haematologica. 2007;92:583-8.3. Musallam KM, et al. Hematologica. 2011;96:1605-12.

Normal liver iron level

● Pulmonary hypertension● Hypothyroidism● Hypogonadism● Endocrine/bone complications

RISK THRESHOLDS3

● Thrombosis● Vascular complications

● Osteoporosis

Mean age ± SD β-TI β-TM

Taher et al. 20101

n

Age (years)

LIC (mg Fe/g dry wt)

19

32.8 ± 7.9

15.0 ± 7.4

19

33.0 ± 7.4

15.7 ± 9.9

Origa et al. 20072

n

Age (years)

LIC (mg Fe/g dry wt)

22

20.0 ± 5.0

11.3 ± 6

22

23.0 ± 10.0

11.8 ± 7

1.8 mg/g dry wt

6 mg/g dry wt

7 mg/g dry wt

9 mg/g dry wt

ICT in NTDT

● Chelation therapy is advisable if liver iron concentration (LIC) 5 mg/g dw

● Direct assessment is desirable; biopsy or MRI

● If LIC measurement is not available, serum ferritin is a reasonable alternative, taking into consideration that serum ferritin may underestimate LIC in TI

SF chelation thresholds

5 mg/g

dw

1000

ng/ml

53%

800

ng/ml

70%NTDT IOL threshold

A serum ferritin of 800 ng/ml increases the sensitivity of detecting thalassemia intermedia patients with iron overload

Investigational use of deferasirox versus placebo: THALASSA study design

Efficacy and safety of deferasirox versus placeboin NTDT patients

Inclusion • Male/female• Aged ≥10 years with NTDT• LIC ≥5 mg Fe/g dw• Serum ferritin >300 ng/mL

Exclusion • Regular transfusion requirement • Chelation therapy prior to entry• HbS thalassemia variants• Impaired renal/liver function

Change in LIC from baseline after 1 year of treatment compared with placebo-treated patients

Taher AT et al. Blood 2012;120(5):970-7

–1.95

–3.80

0.38

Placebo

5 mg/kg/day 10 mg/kg/day

Starting deferasirox dose:1

0

– 1

– 2

– 3

– 4

LIC

ch

ang

e fr

om

ba

seli

ne

to W

eek

52 l

east

sq

ua

res

mea

n (

mg

Fe

/g d

w)

P=0.001*

P<0.001*

P=0.009

*Adjusted P-value with Dunnett’s method


Effect of deferasirox on LIC in THALASSA

Study met its primary endpoint

Effect of deferasirox onserum ferritin in THALASSA

–121

–222

115

Placebo

5 mg/kg/day 10 mg/kg/day

Starting deferasirox dose:

Ser

um

fer

riti

n c

han

ge

fro

m

bas

elin

e to

We

ek 5

2 le

ast

squ

ares

mea

n (

ng

/mL

)

P<0.001*

P<0.001*

P=0.088

150

100

50

0

–50

–100

–150

–200

–250

*Adjusted P-value with Dunnett’s method


Adverse events, n (%)

Deferasirox 5 mg/kg/day

n=55

Deferasirox 10 mg/kg/day

n=55

Placebo overall

n=56

Nausea 3 (5.5) 4 (7.3) 4 (7.1)

Skin rash 2 (3.6) 5 (9.1) 1 (1.8)

Diarrhea 0 5 (9.1) 1 (1.8)

Headache 2 (3.6) 1 (1.8) 2 (3.6)

Upper abdominal pain 2 (3.6) 1 (1.8) 0

Abdominal pain 1 (1.8) 1 (1.8) 1 (1.8)

Most common drug-related adverse events in THALASSA


Splenectomy

● Indications for splenectomy● Poor growth and

development

● Increased transfusion demand

● Symptomatic splenomegaly

● Hypersplenism (leukopenia, thrombocytopenia)


Splenectomy

● Splenectomy increases chances of:● Thrombosis

● Silent brain infarcts

● Extramedullary hematopoiesis

● Pulmonary hypertension

● Leg ulcers

● Iron related endocrinopathies

● Infection


Thromboembolic events in a large cohort of TI patients

● Patients (N = 8,860)

● 6,670 with TM

● 2,190 with TI

● 146 (1.65%) thrombotic events

● 61 (0.9%) with TM

● 85 (3.9%) with TI

● Risk factors for thrombosis:

● age (> 20 years)

● previous thromboembolic event

● family history

● splenectomy

Taher A, Isma'eel H, Mehio G, et al. Thromb Haemost. 2006;96:488-91.DVT = deep vein thrombosis; PVT = portal vein thrombosis; STP = superficial thrombophlebitis.

Thromboembolic events (%)

Typ

e o

f ev

ent

12

8

19

12

39

9

66

30

0

11

8

23

28

48

0 20 40 60 80

Others

STP

PVT

PE

DVT

Stroke

Venous

TM (n = 61)

TI (n = 85)

1Musallam KM, Taher AT. Hemoglobin 2011;35:503–510

Iron chelation

Hydroxyurea

Transfusion

Splenectomy

SF ≥ 1,000 μg/L

Hb ≥ 9 g/dL

Female

Age > 35 years2.59

1.27

0.41

1.86

6.59

0.28

0.56

0.97

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15Adjusted odds ratio for thrombosis

Splenectomy, age above35 years, and a serum ferritin level >1000 μg/L are associated with a

higher risk for thrombosis1

Risk factors for thrombosis in β-TI

The OPTIMAL CARE studysplenectomized patients


EMH Splenectomy 0.44 0.26–0.73 0.001Transfusion 0.06 0.03–0.09 < 0.001Hydroxyurea 0.52 0.30–0.91 0.022

Pulmonary hypertension Age > 35 years 2.59 1.08–6.19 0.032Splenectomy 4.11 1.99–8.47 < 0.001Transfusion 0.33 0.18–0.58 < 0.001Hydroxyurea 0.42 0.20–0.90 0.025Iron chelation 0.53 0.29–0.95 0.032

Heart failure Transfusion 0.06 0.02–0.17 < 0.001Thrombosis Age > 35 years 2.60 1.39–4.87 0.003

Hb ≥ 9 g/dL 0.41 0.23–0.71 0.001Serum ferritin ≥ 1,000 µg/L 1.86 1.09–3.16 0.023Splenectomy 6.59 3.09–14.05 < 0.001Transfusion 0.28 0.16–0.48 < 0.001

Cholelithiasis Age > 35 years 2.76 1.56–4.87 < 0.001Female 1.96 1.18–3.25 0.010Splenectomy 5.19 2.72–9.90 < 0.001Transfusion 0.36 0.21–0.62 < 0.001Iron chelation 0.30 0.18–0.51 < 0.001

Abnormal liver function Serum ferritin ≥ 1,000 µg/L 1.74 1.00–3.02 0.049






Hypogonadism Female 2.98 1.79–4.96 < 0.001Serum ferritin ≥ 1,000 µg/L 2.63 1.59–4.36 < 0.001Transfusion 16.13 4.85–52.63 < 0.001Hydroxyurea 4.32 2.49–7.49 < 0.001Iron chelation 2.51 1.48–4.26 0.001

The OPTIMAL CARE studysplenectomized patients


Splenectomy was independently associated with an increased risk of most disease-related complications

OPTIMAL CARE study: patient stratification according to splenectomy and TEE status

● Three groups of patients identified ● Group I, splenectomized patients with a documented TEE (n = 73)

● Group II, age- and sex-matched splenectomized patients without TEE (n = 73)

● Group III, age- and sex-matched non-splenectomized patients without TEE (n = 73)

Taher A, Musallam KM, Karimi M, et al. J Thromb Haemost. 2010;8:2152-8.

Type of thromboembolic event in splenectomized TI patients (Group I) n (%)

DVT 46 (63.0)

PE* 13 (17.8)

STP 12 (16.4)

PVT 11 (15.1)

Stroke 4 (5.5)

TEE = thromboembolic events.

*All patients who had PE had confirmed DVT.

Parameter Group OR 95% CI p valueNRBC count ≥ 300 x 106/L Group III 1.00 Referent

< 0.001Group II 5.35 2.31–12.35

Group I 11.11 3.85–32.26

Platelet count ≥ 500 x 109/L Group III 1.00 Referent

< 0.001Group II 8.70 3.14–23.81

Group I 76.92 22.22–250.00

PHT Group III 1.00 Referent

0.020Group II 4.00 0.99–16.13

Group I 7.30 1.60–33.33

Transfusion naivety Group III 1.00 Referent0.001Group II 1.67 0.82–3.38

Group I 3.64 1.82–7.30

OPTIMAL CARE study: multivariate analysis of the risk per patient group

NRBC = nucleated red blood cell; PHT = pulmonary hypertension; OR = adjusted odds ratio; CI = confidence interval. Taher A, Musallam KM, Karimi M, et al. J Thromb Haemost. 2010;8:2152-8.

Group I patients had significantly higher NRBC, platelets, and PHT occurrence, and were mostly

non-transfused

Group I patients had significantly higher NRBC, platelets, and PHT occurrence, and were mostly

non-transfused

Time-to-thrombosis (TTT) since splenectomy

Time to thrombosis

Duration since splenectomy (years)

Cu

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0.2

0.4

0.6

0.8

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0 5 10 15 20 25 30 35 40

NRBC count< 300 x 106/L≥ 300 x 106/L


Cu

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0.4

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TransfusedYesNo


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Platelet count< 500 x 109/L≥ 500 x 109/L


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Pulmonary hypertensionYesNo

• The median TTT following splenectomy was 8 years (range 1–33 years)

• The median TTT was significantly shorter in patients with an NRBC count ≥ 300 x 106/L (p = 0.002), a platelet count ≥ 500 x 109/L (p =

0.008), and who were transfusion-naive (p = 0.009)

• The median TTT following splenectomy was 8 years (range 1–33 years)

• The median TTT was significantly shorter in patients with an NRBC count ≥ 300 x 106/L (p = 0.002), a platelet count ≥ 500 x 109/L (p =

0.008), and who were transfusion-naive (p = 0.009)

Taher A, Musallam KM, Karimi M, et al. J Thromb Haemost. 2010;8:2152-8.

Cerebral thrombosis

●Among 30 splenectomized patients with β-TI

● 18 (60.0%) had abnormal MRI findings

● 19 (63.3%) had abnormal PET findings

● 26 (86.7%) had abnormal MRI, abnormal PET, or both

Musallam K et al. Ann Hematol 2012;91:235–241

n (%)

MRI PET Either MRI or PET

Number of lesions*SingleMultiple

4 (13.3)14 (46.7)

5 (16.7)14 (46.7)

8 (26.7)21 (70.0)

Bilateral lesions 13 (43.3) 1 (3.3) 13 (43.3)

LocationFrontalParietalTemporalOccipital

17 (56.7)9 (30.0)1 (3.3)3 (10.0)

3 (10.0)14 (46.7)18 (60.0)0 (0.0)

18 (60.0)20 (66.7)18 (60.0)3 (10.0)

HbF Modulation

● The defective production of β-chains can be compensated for by increased ɣ-chain production to form HbF

● Available HbF modulators include hydroxyurea, 5-azacitidine, decitabine, short-chain fatty acids

● Studies in thalassemia and especially thalassemia intermedia are relatively limited

Association of HbF and morbidity in untransfused patients with β-TI

Ext

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us

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m

Hyp

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on

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m

Ost

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oro

sis

*P<0.001; †P=0.003; ‡P=0.002

*

†

***

*

†‡ ‡

Musallam KM et al. Blood 2012;119:364–367

Use of hydroxyurea for the modulation of HbF in β-TI

● Some debate over long-term efficacy and safety:

● Most adverse effects with low-dose hydroxyurea over the short and medium term are minor and can be tolerated without discontinuation4

● Beneficial effects may be transient and attenuate in the long term5

● Variable results

1Mancuso A et al. Br J Haematol 2006;133:105–106; 2Karimi M et al. J Pediatr Hematol Oncol 2005;27:380–385; 3Dixit A et al. Ann Hematol 2005;84:441–446; 4Karimi M et al. Pediatr Hematol Oncol 2010;27:205–221; 5Rigano P et al. Br J Haematol 2010;151:509–515

Hydroxyurea enables some patients to become transfusion independent or develop marked

increases in Hb levels1–3





Hypogonadism Female 2.98 1.79–4.96 < 0.001Serum ferritin ≥ 1,000 μg/L 2.63 1.59–4.36 < 0.001Transfusion 16.13 4.85–52.63 < 0.001Hydroxyurea 4.32 2.49–7.49 < 0.001Iron chelation 2.51 1.48–4.26 0.001

HU treatment may be protective for complications

Taher AT et al. Blood 2010;115:1886–1892

In the OPTIMAL CARE study, 202/584 patients received hydroxyurea

Hydroxyurea treatment was protective for EMH, PHT, leg ulcers, hypothyroidism and osteoporosis

PHT

● Pulmonary hypertension:● Defined as mean pulmonary artery pressure ≥ 25 mm

Hg at rest with a pulmonary capillary wedge pressure ≤ 15 mm Hg and pulmonary vascular resistance > 3 Wood units

● The pathophysiology has not been extensively studied but NO dysregulation has been speculated

● Sildenafil has been reported in few cases to be effective

● A trial has just concluded to test its effectiveness

● Bosentan (endothelin receptor antagonist) also reported to be effective in one patient

Taher et al. Br J Haematol. 2011;152:512-23.

EMH

● Extramedullary hematopoiesis● Most commonly paraspinal (11-15%) of cases

● Debilitating clinical consequences

● Management● Hypertransfusion

● HbF modulation

● Radiation

● Surgery (laminectomy)

● Individualize treatment


Endocrine complications

● Endocrine complications● High prevalence of 25-hydroxy vitamin D deficiency

● High prevalence of osteoporosis

● Devastating fractures and bone pain

● High doses of calcium and vitamin D supplementation are recommended

● Bisphosphonates have been effective in TM

● No data about bisphosphonates in TI


Pregnancy

● Pregnancy● Delayed puberty is common

● Fertility is usually normal

● Increased risk of abortion, pre-term delivery, IUGR, Caesarean section delivery, thromboembolic events

● Transfusions should be used carefully for fear of alloimmunization

● Splenomegaly can interfere with the enlargement of the uterus

● Anticoagulation should be considered

Taher et al. Brit J Haematol. 2011;152:512-23.

Thrombosis

● Anticoagulation● TI are at high risk of thromboembolic events and

anticoagulation merits consideration

● Thrombocytosis is implicated in the pathophysiology of thrombotic disease

● One study showed lower recurrence rate after treatment with Aspirin but the results were not statistically significant

● Antiplatelet therapy is a logical solution

Taher et al. Brit J Haematol. 2011;152:512-23.

Multimodal therapy

Mean numberof complications

0.83 1.31 1.30 2.00 0.85 2.02 1.54 2.43

Iron chelation

Transfusion

Hydroxyurea Y

Y

Y N

N

Y N

N

Y

Y N

N

Y N

Taher AT, et al. Blood. 2010 ;115:1886-92.

Supportive therapy

• With the increased longevity, patients are growing older with their diseases and suffering more complications which is jeopardizing their QoL.

• Supportive therapy is key to alleviating these ailments

HR-QOL

A longer duration with a known thalassemia diagnosis was the only independent variable correlating with higher Mental Heath Scores (P = 0.039) while multiplicity of clinical complications was the only

independent variable correlating with lower Physical Heath Scores (P = 0.032).

Musallam KM, Khoury B, Abi-Habib R, et al. Eur J Haematol. 2011;87:73-9.

Depression and anxiety in β-TI

● Cross-sectional study - Chronic Care Center in Lebanon

● 80 patients:

● 32 β-TI [median age 24 years]

● 48 β-TM [median age 23 years])

● Patients with TM had significantly longer median duration with a known thalassemia diagnosis than TI patients (P<0.001)

Proportion of patients with different combinations of diagnoses

Considerable proportion of adult patients with TM and TI show evidence of depression and anxiety

Patients with TI are more liable to state anxiety than TM patients of a similar age, that is attributed to a shorter duration of living with a thalassemia diagnosis

Musallam KM, et al. Thalassaemia International Federation 2011.

Depression

8 (10%)

Trait-Anxiety

8 (10%)

State-Anxiety

3 (3.8%)

3 (3.8%) 9 (11.3%)

4 (5%)

8 (8%)

Supportive therapy

• With the increased longevity, patients are growing older with their diseases and suffering more complications which is jeopardizing their QoL.

• Supportive therapy is key to alleviating these ailments

Take home message

● TI, a once overlooked disease, displays a myriad of complications

● Management of TI can be either palliative or curative

● Palliative care involves transfusion and iron chelation therapy or hydroxycarbamide in addition to control of symptoms

● We must always keep in mind the QoL of these patients and provide the proper counseling and supportive therapy

Approaches to management of β-thalassemia intermedia Ali Taher, MD, PhD, FRCP American University...

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