pediatric hematology & oncology-newsletr[1]

8/3/2019 Pediatric Hematology & Oncology-Newsletr[1]

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Vol 1 October 2011l

Editors Take

It is with a sense of great excitement that I write this editorial. This newsletter was conceived keeping in mind the explosion of

knowledge in the field of pediatrics. With the evolution of pediatric subspecialties it has become nigh impossible to keep oneself

abreast of all developments in all fields. Bearing this in mind, we have started this newsletter. We will cover one pediatric sub

specialty in each issue.

The first edition deals with hemato-oncology. Dr Amita Mahajan has reviewed ITP and summarized treatment guidelines while

trying to answer a few pressing management issues. This is followed by a journal scan which takes a look at exciting developments in

the field. A clinical quiz designed to challenge clinicians has been incorporated. In the last section is a case report on Evan's

syndrome, a relatively rare condition which can fox us.

Since this is our first attempt there are bound to be opportunities to improve. Suggestions, criticisms, comments all are welcome

and will be accepted with humility. Till next timehappy reading.

Pediatric Hematology and Oncology

ACAP Newsletter

Indias first internationally accredited hospital

Accredited byJoint Commission International

Chief Patron

Dr. Prathap C. Reddy

ChairmanApollo Group of Hospitals

Patron

Mr. Jaideep Gupta

Managing DirectorIndraprastha Apollo Hospital

ACAP Co-ordinator

Dr. R. N Srivastava

Pediatric Nephrologist

Research Co-ordinator

Dr. Veena Kalra

Pediatric Neurologist

Academic Co-ordinator

Dr. Anjali Kulkarni

Neonatologist

Clinical Co-ordinator

Dr. L. S Arya

Pediatric Hemato-Oncologist

PICU Co-ordinator

Dr. Anita Bakshi

Pediatric Intensivist

NICU Co-ordinator

Dr. Vidya Gupta

Neonatologist

PCCS Co-ordinator

Dr. Vikas Kohli

Pediatric Cardiologist

Training Co-ordinator & Editor

Dr. Amita Mahajan

Pediatric Hemato-Oncologist

Patron

Dr. Anupam Sibal

Group Medical DirectorPediatric Gastroenterologist

Ped Surgery Co-ordinator

Dr. Sujit K. Chowdhary

Pediatric Surgeon and Urologist

Editor

Dr. Akshay Kapoor

Pediatric Gastroenterologist

Dr. R. N. Srivastava

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Vol 1 l October 2011

Immune Thrombocytopenic Purpura: Is there anything new?

Immune Thrombocytopenic Purpura (ITP) is characterised by isolated thrombocytopenia often occurring in the absence of obviousprecipitants. It is a common childhood condition and a number of issues in its management have often posed dilemmas for the

pediatrician and the hematolologist. In 1996, The American Society of Hematology published guidelines for the management of ITP

which became the reference standard for this condition (1). The last few years have seen major strides in our understanding of the

pathophysiology of this condition. There has also been a concerted effort to standardize the terminology, definitions and outcome

criteria (2). In addition, new agents have emerged in the form of thrombopoietic agents. Given the recent advances in both the

understanding and treatment of ITP, earlier this year, the American Society of Hematology published evidence based practice

guidelines for ITP (3). This write-up endeavors to summarize this new information.

Historically, ITP has been believed to be caused essentially due to peripheral platelet destruction. Recent data has shown that

reduced platelet production also plays a significant role in many patients with ITP (4,5). In the past, B cell mediated destruction was

thought to be the predominant mechanism of immune destruction. However the absence of platelet antibodies in up to 50% of

patients, and the ability to achieve remission despite demonstrable antibodies suggested that other mechanisms are likely to beinvolved in the pathophysiology of ITP. There is now considerable evidence that T cells play an important role in ITP (6). It also

appears that a number of currently effective modalities for ITP involve T cell modulation (7).

In 2007, a consensus conference was convened in Vicenza to standardize the terminology. The key recommendations of this

International Working Group published in 2009(2) were :

The term immuneto be used in preference to idiopathicas the immunological basis of this condition has been elucidated in

great detail now.

A platelet count < 100,000 is established as the threshold for diagnosis

Primary ITPto refer to isolated thrombocytopenia in the absence of other causes or disorders associated with thrombocytopenia.

All other forms of immune thrombocytopenia are referred to as Secondary ITP. This distinction is clinically relevant because of the

different natural history and treatment strategies. The management of ITP secondary to an on-going medical condition (4) is

essentially focussed on the management of the underlying disorder. Drug-induced ITP usually remits spontaneously after

withdrawal of the inciting drug but occasionally may require platelet transfusion.

Acute ITPin view of its retrospective nature has been replaced by newly diagnosed ITP i.e within three months from diagnosis.

Persistent ITP refers to thrombocytopenia persisting between 3 to 12 months from presentation and Chronic ITP to

thrombocytopenia beyond 12 months.

Severe ITPrefers to bleeding symptoms at presentation sufficient to mandate treatment, or occurrence of new bleeding symptoms

on follow-up requiring additional therapy.

Complete Response (CR) is defined as any platelet count >100,000. Response (R) is defined as a platelet count between 30,000-

100,000 or doubling of the baseline count. No response (NR) is defined as platelet count


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To treat or not to treat?

This has always been an extremely contentious issue. Given a very low incidence of serious bleeding episodes in children, the

current recommendation is that children with no bleeding or mild bleeding (defined as skin manifestations only i.e. petechiae and

ecchymosis) should be managed with observation alone regardless of platelet count. Rosthoj et al (9) followed 500 children with ITP

for 6 months and found no episodes of intracranial hemorrhage (ICH) or serious bleeding. A registry of 2540 children for 6 months

reported 3 episodes (0.17%) of ICH (10). A recent study enrolling 863 children determined bleeding episodes in the first 28 days

after diagnosis (11). Of these, 505 children had counts


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How best to manage chronic ITP?

Platelet count alone, regardless of the absolute value is not an indication for treatment. Observation alone, if the child is

asymptomatic orv has minimal symptoms is an acceptable option. Bleeding from any site, onset of menarche with menorrhagia,

active participation in athletics may warrant treatment. Treatment options include corticosteroids, IV anti D, rituximab,

splenectomy, cyclosporin, azathioprine, vincristine etc. There is no algorithm for management and treatment has to be

individualised for every child.

Splenectomy : Who? When? How?

Splenectomy remains the most effective therapy for chronic ITP. However, there are obvious concerns regarding splenectomy in

young children. The current guidelines recommend that it may be considered for children with chronic or persistent ITP with

significant bleeding, lack of responsiveness or intolerance to other therapeutic strategies. The mere persistence of a low plateletcount with no or minimal symptoms does not justify a splenectomy. It should be avoided as far as possible for the first 12 months

unless accompanied by severe disease causing severe impairment of quality of life. If selected for splenectomy, it may be done by

open or laparascopic method depending upon the choice of the surgeon. Both offer similar efficacy. It is important to ensure

immunisation with pneumococcal and meningococcal vaccine prior to splenectomy

Thrombopoietic agents in the management of ITP

The last decade or so has seen exciting developments in this area. It has been recognised for some time that decreased platelet

production plays an integral role in the pathophysiology of ITP. The thrombopoietin (TPO) levels in ITP are not or only mildly elevated

in contrast to patients with aplastic anemia. There has been a concerted effort to develop efficacious and safe thrombopoietic

agents or TPO-receptor agonists for some time. The first generation thrombopoietic agents were found to be effective in various

settings but their efficacy was marred by neuralising antibodies. The second generation TPO agonists i.e. Romiplostim andEltrombopag have completed Phase II and Phase III trials and have now been approved for use in ITP though pediatric data is still

small. These molecules have no sequence homology with endogenous TPO hence the propensity to make antibodies is minimal.

In a double blind, randomised controlled trial, romiplostim, a thrombopoietin-mimetic peptibody or placebo were given

subcutaneously weekly to adults with chronic ITP (13). The overall platelet response rate was noted in 88% of non-splenectomised

and 79% of splenectomised patients given romiplostim compared with 14% of non-splenectomised and no splenectomised

patients given placebo (p


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Management of secondary ITP

For patients with ITP secondary to HIV, the child should be treated with antiretroviral therapy before any other treatment. If other

treatment is required, treatment should consist of corticosteroids, IVIG or IV Anti D. For ITP secondary to HCV infection, antiviral

therapy should be considered but with close monitoring as interferon therapy may further drop the platelet count. If immune-

modulating treatment is indicated, IVIG would be the agent of choice. For ITP secondary to H. Pylori, eradication therapy should be

administered.

The current guidelines based on evidence and recent information on pathophysiology as well as the development of new agents

provide practicing clinicians with a broad framework for the management of ITP. However, the management needs to be

individualised for every single child.

George JN, Woolf SH, Raskob GE, et al. Idiopathic Thrombocytopenic Purpura; a practice guideline developed by explicit methods

for the Amerian Society of Hematology. Blood 1996; 88(1): 3-40.

Rodeghiero F, Stasi R , Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune

thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009;113(11):2386-2393.

Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune

thrombocytopenia. Blood 2011; 117(16): 4190-4207.

Stasi R, Evangelista ML, Stipa S ,Buccisiano F ,et al. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology

and management .Thromb Haemost , 2008;994-13.

Cines DB , Bussel JB ,Liebman HA , Prak ETL .The ITP Syndrome: pathogenic and clinical diversity. Blood , 2009; 113,26.

Aboul-Fotoh Lel-M, Abdel Raheem MM,EI-Deen MA ,Osman AM. Role of CD4+CD25+ T cells in children with idiopathic

Thrombocytopenic pupura. J Pediatr Hematol Oncol,2011;33:81-5.

Stasi R , Cooper N, Del Poeta G,Stipa E ,et al.Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenicpurpura receiving B cell depleting therapy with rituximab. Blood ,2008;112:1147-50.

Calpin C, Dick P, Poon A, Feldman W. Is bone marrow aspiration needed in acute childhood idiopathic thrombocytopenic purpura

to rule out leukemia? Arch Pediatr Adolesc Med 1998; 152(4): 345-347.

Rosthoj S, Hedlund-Treutiger I, Rajantie J, et al. Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura

in children: a prospective nordic study of an unselected cohort. J Pediatr 2003;143(3):302-307.

Kuhne T, Buchanan GR, Zimmerman S, et al. A prospective comparative study of 2540 infants and children with newly diagnosed

ITP from the intercontinental childhood ITY study group. J Pediatr 2003;143(5): 605-608.

Neunert CE, Buchanan GR, Imbach P, et al. Severe hemorrhage in children with newly diagnosed ITP. Blood 2008; 112(10):

4003-4008.

Wang J, Wiley JM, Greenberg J, et al. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment.

J Pedaitr 2005; 146(2): 217-221.Kuter DJ, Bussel JB, Lyons RM et al. Efficacy of romiplostim in patients with chronic ITP: a double blind randomised controlled trial.

Lancet 2008; 371(9610): 395-403.

Bussel JB, Buchanan GR, Nugent DJ, et al. A randomised, double blind study of romiplostim to determine its safety and efficacy in

children with immune thrombocytopenia. Blood 2011; 118(1): 28-36.

Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia(RAISE): a 6-month,

randomised phase 3 study. Lancet 2011; 377(9763): 393-402.

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Journal Scan

Red blood cell transfusion in critically ill children : A narrative review.

Although allogeneic blood has become increasingly safer from infectious agents, mounting evidence indicates that RBC transfusions

are associated with complications and unfavorable outcomes. As a result, there has been growing interest and efforts to limit RBC

transfusion, and indications are being revisited and revamped. Although a so-called restrictive RBC transfusion strategy has been

shown to improve morbidity and mortality in critically ill adults, there have been relatively few studies on RBC transfusion

performed in critically ill children. After a brief overview of physiology of oxygen transportation, anemia compensation, and current

transfusion guidelines based on available literature, risks and outcomes of transfusion in general and in critically ill children are

summarized in conjunction with studies investigating the safety of restrictive transfusion strategies in this patient population. The

available evidence does not support the extensive use of RBC transfusions in general or critically ill patients. Transfusions are still

associated with risks, and although their benefits are established in limited situations, the associated negative outcomes in many

more patients must be closely addressed. Given the frequency of anemia and its proven negative outcomes, transfusion decisions in

the critically ill children should be based on individual patient's characteristics rather than generalized triggers, with consideration

of potential risks and benefits and available blood conservation strategies that can reduce transfusion needs.

Outcomes for Children and Adolescents with Cancer: Challenges for the Twenty-First Century

This report provides an overview of current childhood cancer statistics to facilitate analysis of the impact of past research

discoveries on outcome and provide essential information for prioritizing future research directions. Incidence and survival data for

childhood cancers came from the Surveillance, Epidemiology, and End Results 9 (SEER 9) registries, and mortality data were based

on deaths in the United States that were reported by states to the Centers for Disease Control and Prevention by underlying cause.

Childhood cancer incidence rates increased significantly from 1975 through 2006, with increasing rates for acute lymphoblastic

leukemia being most notable. Childhood cancer mortality rates declined by more than 50% between 1975 and 2006. For leukemias

and lymphomas, significantly decreasing mortality rates were observed throughout the 32-year period, though the rate of decline

slowed somewhat after 1998. For remaining childhood cancers, significantly decreasing mortality rates were observed from 1975 to

1996, with stable rates from 1996 through 2006. Increased survival rates were observed for all categories of childhood cancers

studied, with the extent and temporal pace of the increases varying by diagnosis.

Continued success in reducing childhood cancer mortality will require new treatment paradigms building on an increased

understanding of the molecular processes that promote growth and survival of specific childhood cancers.

High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia

The authors evaluated 190 children with very high-risk leukemia, who underwent allogeneic hematopoietic cell transplantation in 2

sequential treatment eras, to determine whether those treated with contemporary protocols had a high risk of relapse or toxic

death, and whether nonHLA-identical transplantations yielded poor outcomes. For the recent cohorts, the 5-year overall survival

rates were 65% for the 37 patients with acute lymphoblastic leukemia and 74% for the 46 with acute myeloid leukemia; these rates

compared favorably with those of earlier cohorts (28%, n = 57; and 34%, n = 50, respectively). The authors concluded thattransplantation has improved over time and should be considered for all children with very high-risk leukemia, regardless of

matched donor availability.

Cord blood iron profile and breast milk micronutrients in maternal iron deficiency anemia.

Micronutrient deficiencies among pregnant women are widespread in low-income countries. Iron deficiency anemia (IDA) is the

most frequent nutritional deficiency during pregnancy, with an impact on maternal and fetal morbidity and mortality. The authors

aimed to evaluate the effect of maternal IDA and nutritional status on birth anthropometry, cord blood iron profile and breast milk

micronutrients in 50 anemic (hemoglobin


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Off-Label Recombinant Factor VIIa Use and Thrombosis in Children : A Multi-Center Cohort Study

A retrospective multi-center cohort study using the Pediatric Health Information System administrative database evaluated the off-

label use of recombinant factor VIIa (rFVIIa) in tertiary care pediatric hospitals across the United States and assessed thrombotic

events. Children 18 years of age or younger who received rFVIIa between 2000 and 2007 were included. A label admission was

defined as an admission with an ICD diagnostic code for hemophilia or factor VII deficiency; admissions without these codes were

classified as off-label. There were 4942 rFVIIa admissions, representing 3764 individual subjects; 74% (3655) of the admissions were

off-label. There was a 10-fold increase in the annual rate of off-label admissions from 2000 to 2007 ( P < .001). The mortality rate in

the off-label group was 34% (1258/3655). Thrombotic events occurred in 10.9% (399/3655) of the off-label admissions.The off-label

use of rFVIIa in hospitalized children is increasing rapidly despite the absence of adequate clinical trials demonstrating safety and

efficacy. Thrombotic events are common and mortality is high among patients receiving off-label rFVIIa. Further studies are

warranted to determine whether these adverse events are attributable to rFVIIa.

Venous Thromboembolism in children: Epidemiologic data from a pediatric tertiary care center in Alabama

Venous thrombosis is an infrequent but serious cause of hospitalization in children. The epidemiology and natural history remains

incompletely defined. The authors evaluated thrombosis in a single children's hospital over a 3-year period. Of 41,906

hospitalizations, 92 children were identified for review. The incidence of thrombosis was 0.22%. Locations of thrombosis included

deep venous (51%), pulmonary (21%), renal vein (8%), intrahepatic (8%), and intracranial (12%). Risk factors for thrombosis

included central catheter (32%), malignancy (18%), systemic infection (21%), neurologic disability (9%), cardiac (4%), nephrotic

syndrome (3%), and autoimmune (6%). Six of 92 patients (7%) had thrombophilia. Positive family history of venous

thromboembolism (VTE) or thrombophilic disorder predicted an abnormal test. Treatment included LMW heparin (n=53),

coumadin (n=12), heparin (n=10), tissue plasminogen activator (n=6), argatroban (n=1), thrombectomy (n=2), inferior vena cava

filter (n=2), and no treatment (n=23). Seventy-seven percent demonstrated resolution of the VTE, 14% had persistent or recurrent

VTE, and 9% died. Causes of death were malignancy, prematurity, septicemia, and congenital heart disease. The authors conclude

that venous thrombosis is a serious comorbidity in hospitalized children.

Impact of early transcranial doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell

anemia cohort

Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion

programs significantly reduce stroke risk in patients with abnormal TCD. The authors describe the predictive factors and outcomes

of cerebral vasculopathy in the Crteil newborn SCA cohort (n = 217 SS/S0), who were early and yearly screened with TCD since

1992. MR/ MR angiography was performed every 2 years after age 5. A transfusion program was recommended to patients with

abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell

transplantation to those with HLA-genoidentical donor. Mean follow-up was 7.7 years. The cumulative risks by age 18 years were1.9% for overt stroke, 29.6% for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% for stenosis and 37.1%

for silent stroke by age 14. Cumulating all events, the cerebral risk by age 14 was 49.9%; the independent predictive factors for

cerebral risk were baseline reticulocytes count and LDH level. Thus, early TCD screening and intensification therapy allowed the

reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests

the need for more preventive intervention.

Using Thrombophilia Testing to Determine Anticoagulation Duration in Pediatric Thrombosis is not Cost-Effective

The study was designed to address the cost-effectiveness of thrombophilia testing and treatment strategies among children with a

first episode of thrombosis. A 2-year Markov model was developed to evaluate the cost-utility of 3 strategies: (1) no testing,

anticoagulate for 3 months, (2) no testing, anticoagulate for 6 months, and (3) testing, anticoagulate 3 or 6 months, based on results.

Total costs per patient were $7900 for no test, treat for 3 months; $8900 for test, treat based on results; and $12 100 for no test, treat

for 6 months. Three months of treatment without testing was the least expensive strategy and also the most effective (1.74 quality-

Wiltmer CM, Huang YS, Lynch K, et al. J Pediatr 2011; 158(5):820-825

Wright J M, Watts, Raymond G. J Ped Hematol Oncol 2011; 33 (4): 261-264

Bernaudin F, Verlhac S, Arnaud C et al. Blood 2011;117(4): 1130-40.

O'Brien SH, Smith KJ. J Pediatr 2009;155(1): 100-104

Journal Scan

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-adjusted life-years) by 0.01 to 0.03 quality-adjusted life-years. Cost-utility ratios were sensitive to variation in hospitalization and

medication costs, but 3 months, no testing, always remained the preferred choice. The authors concluded that universalthrombophilia testing after a first episode of thrombosis is not cost-effective when used solely to determine anticoagulation

duration. Therefore, a full panel of thrombophilia studies does not need to be an automatic response at the time of any deep venous

thrombosis diagnoses.

Journal Scan

A clinical quiz - case scenario

A 12 year old girl presented with history of fever off and on with severe pain in the hip and both legs of 4 months duration. She was

unable to ambulate in view of the pain and had been bedridden for weeks. Clinical examination was essentially normal.

Specifically, there was no adenopathy or organomegaly. Investigations revealed a normal blood count, peripheral smear, liver

function and renal function. Erythrocyte sedimentation rate was only mildly elevated. Calcium, Phosphate and Alkaline

phosphatase were normal. Uric acid and lactate dehydrogenase were mildly elevated. Mantoux test was negative. Bone marrow

aspiration was normal.

Radiograph of the hip revealed multiple lytic lesions. Similarly multiple lytic lesions were seen on the skull X ray. Bone scan showed

no significant uptake but PET scan revealed significant uptake in the skull bones, pelvic bones and heads of both humerus.

What could be the possible diagnosis?

For replying to quiz email us : [email protected]

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Introduction

Case report

Discussion

Evans syndrome is a rare autoimmune disease characterised by autoimmune haemolytic anemia and idiopathic thrombocytopenicpurpura in the absence of any underlying etiology (1). It is a potentially a life threatening condition and the typical clinical course is

chronic, relapsing and generally progressive and poor. Mortality is high in the 4 reported pediatric series, ranging from 7-36% (2-4).

The management of Evans syndrome is challenging, with prednisone being, the most commonly used first-line therapy. This often

effectively controls acute episodes, although relapses are frequent when patients are weaned off prednisone. Other therapies

include IVIG, danazol, cyclosporine, azathioprine, cyclophosphamide, and vincristine. Recently, Rituximab (a chimeric

human/mouse monoclonal antibody which targets CD20 on B lymphocytes) has been used in the management of refractory

patients. Long term remissions induced by splenectomy are less frequent, thus imposing the challenge to the haematologist to pick

the best possible option for each patient.

A two year old male child presented to us with history of recurrent thrombocytopenia since the age of 4 months. He hadbeen

receiving steroids intermittently since then and the platelet counts had been fluctuating. He also had complaints of fever on and off

for the past 1year and progressive pallor since 2 months with lowest haemoglobin 2.3. prior to referral, he had received packed red

cells of 5 occasions over a one month period due to severe anemia. He had already been receiving steroids for a few days prior to

admission with poor response. On examination, he had marked hepatosplenomegaly. His initial blood count revealed hemoglobin-

3.4g/dl, Total leucocyte count -6000/ul and platelet count of 20000. Liver and renal function tests were normal. Serum LDH (Lactate

Dehydrogenase) was very high was very high (957IU/L), direct antiglobulin test was strongly positive (DAT3+), indirect coombs test

was negative and reticulocyte count was 18%. On the basis of the presence of immune haemolysis with thrombocytopenia, he was

labelled as Evans syndrome. Screening for autoantibodies was negative. The child was started with Inj Rituximab in a dose

375mg/m2/dose weekly for 4 doses. Steroids were gradually tapered. He responded well with gradual increase in haemoglobin and

platelet count and is currently transfusion free on follow up.

Evans syndrome is a diagnosis of exclusion. Confounding disorders, such as infections, rheumatologic diseases, and malignancies

can present with autoimmune cytopenias, must be ruled out. Patient presents with signs of thrombocytopenia and signs of anemia.

In a national survey, thrombocytopenia and anemia have seen at presentation in 76% and 67% respectively.(5).In addition, 24% of

patients had neutropenia, and 14% had pancytopenia. The etiology of Evans syndrome is unknown. Non crossreacting

autoantibodies are directed against antigens specific to red cells, platelets, or neutrophils. Wang et al demonstrated decreased

levels of serum immunoglobulin (Ig) G, IgM, and IgA in these patients.(6,7) The cytopenias that occur with Evans syndrome may be

related to T-cell abnormalities because decreased T-helper cells and increased T-suppressor cells have been noted in these patients.

The management of Evans syndrome is challenging. Although almost all patients require multiple treatment during the course of

the disease, the search for a consistent, effective, and nontoxic therapy continues. Response to therapy varies even within the same

individual, and the disease is characterized by periods of remission and exacerbation. No randomized trials have been conducted in

patients with Evans syndrome, and the evidence for treatment is based on case reports, case series, and retrospective studies.

Prednisone therapy, the most commonly used first-line therapy, often effectively controls acute episodes, although relapses may be

frequent when patients are weaned off prednisone. Intravenous immunoglobulin (IVIG) may help patients who are dependent on

steroids (8, 9).Other therapies effective include danazol, cyclosporine, vincristine, azathioprine and cyclophosphamide. In an acute

setting, blood transfusions and platelet transfusions may be required to decrease symptoms, although their use should be

minimized. The role of splenectomy is controversial, but it may improve blood counts and reduce steroid dependence, relapses are

common and in most cases, occur within 1-2 months postsplenectomy. Children with Evans syndrome appear to have a higher risk

of postsplenectomy sepsis, especially children with pancytopenia.

Autologous and allogeneic stem cell transplantation have been used in a small number of patients (14 patients aged 5-52 y), with

mixed results (10). Recently, rituximab (a chimeric human monoclonal antibody which targets CD20 on B lymphocytes) has been

used in the management of refractory patients (11,12,13,14). Norton and Roberts reviewed the use of rituximab in 18 patients aged

0.3-65 y (15). The overall response rate with Rituximab in both the studies was encouraging. Rituximab destroys both normal and

malignant B cells that have CD20 on their surfaces, and is therefore used to treat diseases which are characterized by having too

many B cells or dysfunctional B cells (16). Complications associated with rituximab in these studies have been minimal, the mostcommon being infusion-associated reaction.

Evans Syndrome : A Novel Approach to Treatment

Dr. Lalit Mittal

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Conclusion

References

Rituximab offers a novel approach to the management of Evans syndrome. Though in these studies so far, no serious toxicity

has been occurred, one has to be aware that rituximab may be associated with serious adverse events, the most devastating

being progressive multifocal leukoencephalopathy.

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Pui CH, Wilimas J, Wang W. Evans syndrome in childhood. J Pediatr 1980;97:754-8.

Mathew P, Chen G, Wang W. Evans syndrome: Results of a national survey. PediatrHematolOncol 1997;19:433-7.

Suvasan S, Warrier I, Ravindranath Y. The spectrum of Evans' syndrome. Arch Dis Child 1997;77:245-8.

Mathew P, Chen G, Wang W. Evans syndrome: results of a national survey. J Pediatr Hematol Oncol 1997;19(5):433-7.

Wang W, Herrod H, Pui CH. Immunoregulatory abnormalities in Evans syndrome. Am J Hematol 1983;15(4):381-90.

Wang WC. Evans syndrome in childhood: pathophysiology, clinical course, and treatment. Am J Pediatr Hematol Oncol.

1988;10(4):330-8.

Blanchette VS, Kirby MA, Turner C. Role of intravenous immunoglobulin G in autoimmune hematologic disorders.

Semin Hematol. 1992; 3 (Suppl 2):72-82.

Nuss R, Wang W. Intravenous gamma globulin for thrombocytopenia in children with Evans syndrome. Am J Pediatr

Hematol Oncol 1987;9(2):164-7.

Raetz E, Beatty PG, Adams RH. Treatment of severe Evans syndrome with an allogeneic cord blood transplant.

Bone Marrow Transplant 1997;20(5):427-9.

Galor A, O'Brien T. Rituximab treatment for relapsed autoimmune haemolytic anemia in Evans syndrome. Int J Hematol

2003;78(4):335-6.

Mantadakis E, Danilatou V, Stiakaki E, Kalmanti M. Rituximab for refractory Evans syndrome and other immune-mediated

hematologic diseases. Am J Hematol 2004;77(3):303-10.

Zecca M, Nobili B, Ramenghi U, et al. Rituximab for the treatment of refractory autoimmune hemolyticanemia in children.

Blood 15 2003;101(10):3857-61.

Shanafelt TD, Madueme HL, Wolf RC, Tefferi A. Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic

purpura, autoimmune hemolyticanemia, and Evans syndrome. Mayo Clin Proc 2003;78 (11):1340-6.

Norton A, Roberts I. Management of Evans syndrome. Br J Haematol. 2006;132:125-137.

Teachey DT, Manno CS, Axsom KM, et al. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal

autoimmune lymphoproliferative syndrome (ALPS). Blood 2005;105(6):2443-8.

For suggestions & comments email us : [email protected]

Evans Syndrome : A Novel Approach to Treatment

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