Review of recent advances in hematological disorders and treatment

1. JOURNAL CLUB
MODULE: HEMATOLOGY
DR. SADIA BATOOL
RESIDENT GMT2,PIMS

2. STUDY: 1
• Amifostine and rituximab in refractory immune thrombocytopenia : A case series

3. OBJECTIVE
• Management of refractory ITP can be challenging,amifostine, a thiophosphate
prodrug induces mega karyocyte maturation.
• In 2010,Fan et al. published results for 21 Chinese splenectomized patients,aged
13-92,with steroid refractory ITP. Nineteen patients achieved remission 2 months
post-amifostine
• This is the first publication utilizing amifostine and rituximab in refractory ITP.

4. MATERIALS AND METHODS
• At the Cairns hospital in Australia,five patients were identified who were treated with
amifostine and rituximab for refractory ITP.
• Amifostine IV 400mg once daily was administered 5 days per week for 5 weeks.
• Rituximab was administered concurrently with/preceding amifostine based on clinician
preference.
• Data were obtained through medical records and follow up serology up to 5 years post
amifostine was available.

5. RESULTS
• Three case demonstrated durable responses up to 5 years’ follow up.
• One patient initally achieved remission but relapsed 1 year post amifostine.
• One patient who did not have a splenectomy prior to amifostine did not
respond.

6. CONCLUSION
• Three out of five patients achieved durable responses with amifostine and
rituximab. Although there is confounding by rituximab ,given its established low
durable response rate,it is likely that the excellent long term responses achieved
were a result of amifostine.
• Clinical trials with larger patient cohorts and further investigations are required to
confirm the efficacy and mechanism of amifostine in ITP.

7. STUDY: 2
Comparison of splenectomy and Eltrombopag treatment in the second line
treatment of immune thrombocytopenic purpura.

8. OBJECTIVE
• Primary ITP is an acquired autoimmune disease characterized by isolated
thrombocytopenia.
• While first line treatments focus on inhibiting autoantibodies and platelet
destruction,second and third lline treatments include splenectomy and
thrombopoietin receptor agonists.
• In this study aim was to compare efficiency and toxicities of splenectomy and
eltrombopag as second line treatments in ITP.

9. MATERIALS AND METHODS
• Retrospectively analyzed patients who were diagnosed with ITP and followed
between 2015 and 2020.
• Patients who underwent splenectomy or received eltrombopag treatment as
second line or further therapy were included.

10. RESULTS
• There were 38 patients in the splenectomy group and 47 patients in the
eltrombopag group.
• Mean age; 43.2 and 50.5
• Time to response was significantly shorter in the splenectomy arm (0.001).
However response rates at 3rd,6th,12th and 24 months did not exhibit a statistically
significant difference.
• Eltrombopag treatment was ceased for 20 patients after a median of 54.1 months
(range 1-151).among them 12 patients (60%) did not experience a loss of
response.

11. CONCLUSION
• Comparing the splenectomy and eltrombopag arms,even though time to achieve
response was in favor of splenectomy group,this advantage disappeared when
overall response rates and response rates at the 2nd year were considered.
• using eltrombopag in the second or 3rd line therapy does not yield any difference
in terms of time to achieving response.

12. STUDY:3
Efficacy and safety of Roxadustat for anemia in dialysis dependant and non dialysis
dependant chronic kidney disease patients, a systemic review and meta analysis

13. AIMS
• Renal anemia is a common complication of CKD. Roxadustat is the first in class
oral hypoxia inducible factor prolyl hydroxylase inhibitor for the treatment of
anemia.
• In this systematic review,we aimed to investigate the efficacy and safety of
Roxadustat in the treatment of anemia in CKD patients.

14. METHODS
• Pubmed,Cochrane library.Embase and clinical trials.gov databases were searched
from their inception to feb, 2021 for randomized controlled trials (RCTs) that
compared the safety and efficacy of Roxadustat to those of an erythropoiesis
stimulating agent or a placebo in treating anemia in CKD patients.

15. RESULTS
• Nine RCTs involving 2743 patients were found. The meta-analysis showed that
roxadustat increased haemoglobin (Hb) level by 0.91 g/dL (95% confidence interval
[CI]: 0.47-1.34, P < .05), transferrin level by 0.50 mg/dL (95% CI: 0.34-0.65, P < .05),
and total iron-binding capacity by 50.64 μg/dL (95% CI: 36.21-65.07, P < .05) in CKD
patients. Decreases in hepcidin (mean difference [MD] = -23.16, 95% CI: -37.12 to -
9.19, P < .05) and ferritin (MD = -38.35, 95% CI: -67.41 to -9.29, P < .05) levels were
also observed.
• There was no significant difference in the incidence of adverse events (AEs) (OR: 1.12,
95% CI: 0.95-1.32, P = .17) between the roxadustat and control groups; however, the
incidence of serious AEs in the roxadustat group was significantly higher than that in
the ESA group (OR: 1.33, 95% CI: 1.06-1.68, P < .05).

16. CONCLUSION
• Roxadustat can significantly improve renal anaemia in CKD patients by increasing
Hb level and iron metabolism. However, attention must be paid to the risk of SAEs
during treatment.

17. STUDY: 4
• Meta analysis of treatment with rabbit and horse antithymocyte
globulin for aplastic anemia

18. INTRODUCTION
• Aplastic anemia is an immune mediated bone marrow disorder that is associated
with bone marrow cell destruction and peripheral blood pancytopenia.
• Hematopoeitic system cell transplantation is recommended for young patients.
• ATG and cyclosporin are used in combination as s standard immunosuppressive
regimen.
• ATG is a polygonal immunoglobulin that is produced by animals immunized by
specific antigens.

19. MATERIALS AND METHODS
• Non randomized controlled trials and prospective and retrospective cohort
studies in addition to RCTs were included.
• It included clinical studies that compared two or more different ATG regimens for
aplastic anemia as the first line treatment for aplastic anemia.
• Published literature in pubmed from 1946-2014, Cochrane library from inception
to june2014,the web of science from 1980 to 8th june2014 was used.
• The clinical outcomes of rabbit ATG and horse ATG were compared.

20. • The primary outcome measure was the early mortality at 3 months after
treatment with ATG.
• Secondary outcome measure was overall response rate at 6 months.
• OVERALL RESPONSE: blood count recovery not meeting the severe aplastic
anemia criteria and transfusion independancy.

21. RESULTS
• The number of studies that used lymphoglobulins and ATGAM were 8 and 2
respectively.
• Early mortality was 7.5% 55 in 734 patients) in thymoglobulin group and 4.1% (33
in 798 patients) in lymphoglobulin group. (P= 0.016)
• Overall response was obtained from 10 studies,seven studies used
lymphoglobulins as horse ATG and 3 used ATGAM.
• Overall response at 6 months was significantly higher in lypmhoglobuline/
ATGAM than in thymoglobulin group. (RR 1.27; 95% CI 1.05-1.54, P=0.014)