PEDIATRICS IN GENERAL PRACTICE

Guest Editor: Bhim S. Pandhi

Common Hematological Disorders in Children

Deepak Bansal & Sidharth Totadri

Received: 14 March 2013 /Accepted: 20 June 2013 /Published online: 11 August 2013# Dr. K C Chaudhuri Foundation 2013

Abstract It is common for primary care physicians to befaced with children with hematological disorders in everydaypractice. The article seeks to provide realistic information forthe first-contact physician in handling common hematologicaldiseases in children. Practical step-wise approach to under-standing and investigating anemia and bleeding disorders isillustrated. Requirement of iron in normal children and man-agement of iron deficiency anemia (IDA) and thalassemia isexplained. The gold standard for IDA continues to be ferroussulphate which has good bioavailability and is inexpensive.There is emerging concept of delayed clamping of umbilicalcord at birth, particularly in regions with widespread IDA, toaugment iron stores in infancy. Typical case scenarios ofchildren with immune thrombocytopenia (ITP) and hemophil-ia are provided to facilitate the understanding of managementin day to day practice. The vital role of themedical practitionerin shared care of patients with acute lymphoblastic leukemiaand febrile neutropenia is emphasized. A risk based treatmentalgorithm for febrile neutropenia is provided.

Keywords Blood . Cancer . National iron plus initiative .

Nutritional anemia

Introduction

Children constitute a considerable volume of patient load ingeneral practice. Though infections are more commonly en-countered, it is not uncommon to come across children withhematological disorders. The article seeks to provide realisticinformation for the family physician in handling hematologicaldiseases in children. A practical approach to managing anemia

and bleeding diathesis is described. Management of commonhematological illnesses, including iron deficiency anemia, thal-assemia, immune thrombocytopenia (ITP), hemophilia, acuteleukemia and febrile neutropenia is outlined.

Anemia

Anemia is the most common hematological finding encoun-tered in the practice of pediatricians and general practitionersalike. Though the etiology is wide, a rational approach includ-ing history, examination and a reliable hemogram can lead to adiagnosis in the majority. Age of the child offers the first clue:nutritional anemia is typical after 6 mo of age, particularly in asetting of prolonged breast feeding and delayed introductionof solid food. A simplified approach is illustrated in Fig. 1.

A hemogram (Hb, total leucocyte and differential count,platelet count) from a laboratory equipped with an electroniccell counter is recommended rather than a manual count. Ahemogram from a cell counter is more informative, reliableand value for money, than a manual count. In the authors’experience, a manual blood count from less well equippedlab is typically unreliable and often misleading. Mean cor-puscular volume (MCV) and red cell distribution width(RDW) is a measure of red cell size and cell size variability(anisocytosis), respectively. They are readily available froma cell counter report and often aid in diagnosis (Table 1) [2].

Iron Deficiency Anemia (IDA)

How Common is Iron Deficiency?

Iron deficiency is the most common nutritional disorder in theworld. According to National Family Health Survey-3 (2005–06), 79 % of children in the age group of 6 mo to 3 y wereanemic in India [3]. Seven out of every 10 children aged 6–

D. Bansal (*) : S. TotadriPediatric Hematology-Oncology Unit, Department of Pediatrics,Advanced Pediatric Centre, Post Graduate Institute of MedicalEducation and Research, Chandigarh 160012, Indiae-mail: deepakbansaldr@gmail.com

Indian J Pediatr (January 2014) 81(1):42–50DOI 10.1007/s12098-013-1159-8

59 mo in India are anemic– 3 % are severely anemic, 40 % aremoderately anemic, and 26 % are mildly anemic. In contrast, inUSA, 2.1 % children in the age of 1–3 y were found to haveIDA in the period 1999 to 2002 [4].

How to Diagnose IDA?

Anemia is microcytic, hypochromic [low MCV and meancorpuscular hemoglobin (MCH)] with increased RDW. Iron

studies are expensive and seldom required. A therapeutic trialwith iron is often easy and practical.

How to Treat IDA?

Three to six mg/kg/d of elemental iron in 2–3 divided dosesis recommended. Once daily dose may be equally effective.It is good to instruct rinsing of mouth after syrup to avoidstaining of teeth. Parents should be told not to interrupttherapy for minor inter-current ailments. Authors do notprefer highlighting GI adverse effects, as these are uncom-mon in children. Iron is continued for 2 mo following nor-malization of Hb to replace stores. Excess milk and relativelack of solid food is a common underlying cause, whichshould be rectified. Patient should be deformed [5].

Which Iron Preparations Should be Prescribed?

Large numbers of commercial preparations are available thatcompanies aggressively market on presumed benefits. The

No

Bleeds/Thrombocytopenia

Anemia

Yes

NoYes

Organomegaly Organomegaly

Yes No

Nutritional anemiaCeliac diseaseBlood lossRed cell aplasia

Hemolytic anemia: ThalassemiaAcute leukemiaMalaria

Acute leukemiaAplastic anemiaMegaloblastic anemiaITP (If anemia proportionate to bleeds)

Acute leukemiaMalariaHLH

With unconjugated jaundice

Hemolytic anemia: HS, G6PD deficiency,Thalassemia, auto-immune hemolytic anemia Malaria Snake envenomation

Fig. 1 Differential diagnosis of common causes of anemia in children [1]. HLH Hemophagocytic lymphohistiocytosis; ITP Immune thrombocy-topenia; HS Hereditary spherocytosis

Table 1 Normal hemoglobin and MCV during childhood [2]

Age Hemoglobin (g/dL) MCV (fL) Lowest

Mean Range

Cord blood 16.8 13.7–20.1 110

2 wk 16.5 13.0–20.0

3 mo 12.0 9.5–14.5

6 mo–6 y 12.0 10.5–14.0 70–74

7–12 y 13.0 11.0–16.0 76–80

Indian J Pediatr (January 2014) 81(1):42–50 43

gold standard continues to be ferrous sulphate which has goodbioavailability and is inexpensive. Govt. of India supplies fer-rous sulphate syrup (5 mL = 20 mg elemental iron + 0.5 mgfolic acid), pediatric strength tablets (20 mg elemental iron +0.1 mg folic acid) and adult strength tablets (100 mg elementaliron + 0.5 mg folic acid), free of cost. Ferrous fumarate istasteless and stable in syrup as compared to sulphate. A com-bination of iron with ascorbate increases iron absorption, how-ever at the cost of more adverse effects, therefore carrying littleadvantage. Heme based preparations, Ferric ammonium citrateand iron polymaltose complex may be less efficacious. It is agood practice to check labels, as a variety of strengths areavailable. Parenteral iron is almost never indicated.

Do ‘Normal’ Children Need Iron?

American academy of Pediatrics recommends iron supple-ments from 4 completed months of age in healthy, term,breastfed infants (1 mg/kg/d), until appropriate iron-containing complementary foods are introduced [4]. Iron canbe started as early as 2 wk in preterm babies who are toleratingfull feeds, at a dose of 2–3 mg/kg/d and continued till 1 y [6].

What is National Iron Plus Initiative?

The Ministry of Health and Family Welfare has taken apolicy decision to develop the National Iron+ Initiative [7].For all children aged 6 to 60 mo, it is proposed that Iron folicacid (IFA) supplement will be administered under the directsupervision of an Accredited Social Health Activist (ASHA)on fixed days on a biweekly basis. Tablets containing 45 mgof elemental iron and 400 mcg of folic acid would be givenonce a week throughout the 5–10 y period. In addition,Albendazole (400 mg) tablets for de-worming are to beadministered twice a year. Adolescents (10–19 y) will begiven supervised weekly IFA supplementation (100 mg ele-mental iron and 500 mcg folic acid) throughout the year.Disciplined implementation at the grass root level would benecessary for the success of the ambitious, though criticallydesired program.

Does IDA Affect Cognitive Performance?

Iron deficiency adversely affects brain maturation. Iron de-ficient children have suboptimal developmental scores andintelligence quotients which improve variably with iron sup-plementation [8].

What if There is Suboptimal Response to Iron?

It should prompt a re-evaluation for compliance, dose ormalabsorption. Celiac disease must be excluded in refractoryIDA. Typical GI symptoms may be lacking [9].

Does Timing of Umbilical Cord Clamping at Birth InfluenceIron Stores?

Holding the baby 10–15 in. below the introitus in vaginaldeliveries and below the level of the incision in cesareansections; and delaying the cord clamping for 30–60 s afterbirth increases the blood volume in the newborn. It augmentsthe iron stores in the vulnerable period of infancy. Evidenceexists to support delayed cord clamping in preterm infants,when feasible; the single most important benefit is the pos-sibility for a nearly 50 % reduction in intraventricular hem-orrhage. For term infants it may be particularly beneficial inpopulations in which iron deficiency is prevalent [10].

Thalassemia

Diagnosis

The average carrier rate of β thalassemia in India is 3.3 %.Thalassemia major typically manifests in the second half ofinfancy with anemia and hepatosplenomegaly. Hemolyticfacies is noticeable in older children. Anemia is microcytichypochromic. Target cells and nucleated red blood cells aregood clues in the peripheral smear. Confirmation is by Hbelectrophoresis or high performance liquid chromatography(HPLC) of a pre-transfusion blood sample that will demon-strate elevated HbF [11].

Blood Transfusion

Packed red blood cells are transfused at 2–5 weekly intervals,with a goal to maintain pre-transfusion Hb of ≥9 g/dL. 15–20 mL/kg of blood is transfused over a period of 2–3 h. 1–2units are appropriate in older children. No transfusion shouldtake >4 h because of risk of bacterial proliferation at roomtemperature. Diuretics are required only when Hb has beenvery low, for a prolonged period. Blood should not be storedin the everyday refrigerator, as the temperature is uncon-trolled. A unit collected in the previous 2 wk is preferred. Abed side leucocyte filter is desirable, though not mandatory, toreduce the incidence of febrile non-hemolytic transfusion re-actions. Transfusion from first degree relatives is not recom-mended, because of risk of: 1) Transfusion associated graft-versus-host-disease, 2) Failure of a subsequent bone marrowtransplant due to HLA alloimmunization [12].

Iron Chelation Therapy

Blood is a necessary evil. With successive transfusions, thereis progressive accumulation of iron that results in damage tothe heart, liver and endocrine organs. Iron chelation must beinitiated after 10 transfusions or when serum ferritin exceeds

44 Indian J Pediatr (January 2014) 81(1):42–50

1000 ng/mL [11]. Death is inevitable by ~20 y, if iron chela-tion is lacking in patients who are multi-transfused. Threedrugs for iron chelation are available: Desferrioxamine,Deferasirox and Deferiprone [13]. The choice of a chelatoris individualized based on iron overload, compliance, adverse-effects and finances.

Golden Rules of Management

The two rules for optimal care in thalassemia major are: 1)Maintain pre-transfusion Hb of ≥9 g/dL and 2) Regular ironchelation to maintain serum ferritin <1000 ng/mL [11]. Thiswill obviate majority of the complications that are otherwisecommon.

Prevention

As a public health message in regions with high carrier rate,it is wise to recommend thalassemia screening of the wife(followed by husband, if wife is a carrier), well beforeplanning pregnancy. Inheritance is autosomal recessive; thusthere is a 25 % risk of a child being born with thalassemiamajor in each pregnancy when both parents have thalassemiaminor. Antenatal diagnosis by 12 wk by chorionic villoussampling, or 16 wk by amniocentesis is available at severalcenters. Medical termination of pregnancy is suggested if thetest is positive for thalassemia major in the growing fetus.

Stem Cell Transplant

Permanent cure is by hematopoietic stem cell transplant [11].Best donor is an HLA matched sibling. Success ranges from70 to 90 %. Ideal candidate is a young patient with no ironoverload. There is ~25 % chance of an HLAmatch with eachsibling. The cost may vary from Rs. 5–15 lakhs, or more,depending on center and complications. Services formatched unrelated transplant are likely to increase in Indiain near future. Although results for cord blood transplant areencouraging from selected centers in the world, it has a lowersuccess due to low cell dose and delayed engraftment. Theoption of transplant must be offered to all patients, withtimely referral to centers offering such services. In thelong-term, the cost involved in transplant is much lower, ascompared to life-long transfusions and iron chelation.

Thalassemia Intermedia

These are the patients with a less severe disease as comparedto those with thalassemia major. Distinction is clinical.Children who present late (>2 y) and tend to maintain aHb>7 g/dL without overt bony changes and growth failurebelong to this category. They may benefit with oral hydroxy-urea [11].

Bleeding Disorders in Children

A bleeding child is a cause of great concern and often panic,for parents and physician alike. At the outset, it should beidentified whether bleeding is due to a local cause or result ofa systemic bleeding disorder. Typically, recurrent bleedingfrom a single site is likely to have a local etiology (e.g.,trauma, surgery) and concurrent bleeding from multiple sitesis usually due to a systemic bleeding disorder. Self-limitingisolated recurrent epistaxis, particularly in young boys isoften due to frequent nose picking and detailed investiga-tions are unwarranted. Similarly, it is uncommon for a bleed-ing disorder to present as recurrent isolated hematuria. Fre-quent bruises limited to the shin are often physiological.

Based on etiology, bleeding diathesis can be categorizedinto disorders affecting platelets or the coagulation cascadeand can be inherited or acquired. Common inherited disor-ders are Hemophilia A/B and von Willebrand disease(VWD). Inherited disorders usually present in early child-hood. Children often appear well, besides bleeding. Theremay be history of similar illness in family members. Ac-quired disorders include immune thrombocytopenia (ITP),liver disease, vitamin K deficiency, disseminated intravascu-lar coagulation, etc. Typically, these patients present with arelatively short history and tend to be unwell except in ITP[14]. An approach to investigate bleeding disorders is outlinedin Table 2 and Fig. 2. Bleeding and clotting time tests arelargely obsolete.

Immune Thrombocytopenia (ITP)

ITP refers to ‘immune thrombocytopenia’ and not ‘idiopathicthrombocytopenic purpura’. The term ‘immune’ has replaced‘idiopathic’, highlighting the immune-mediated mechanismof the disease. The term ‘purpura’ has been omitted as bleed-ing symptoms are absent or minimal in a large proportion ofcases. The ‘P’ in ITP, has been retained to avoid altering thetraditional acronym, and is now the abbreviation for ‘penia’ –so the new name ‘Immune thrombocytopenia’. ITP is a rela-tively common condition causing bleeding in an otherwisenormal child. It is characterized by autoimmune destruction ofplatelets in response to an unknown stimulus. Based on theduration of thrombocytopenia, ITP is classified as newlydiagnosed (diagnosis to 3 mo), persistent (3 to 12 mo fromdiagnosis), or chronic (>12 mo). The term ‘acute ITP’ hasbeen omitted because of vagueness and retrospective defini-tion and has been replaced by ‘newly diagnosed ITP’ [16].

Case Scenario 1

A 4-y-old boy is brought to OPD with abrupt onset of bluishspots on the skin for 2 d. Transient ooze from gums wasreported following brushing. He is active and playful and not

Indian J Pediatr (January 2014) 81(1):42–50 45

on any medications. Examination is normal apart from mul-tiple petechiae and purpurae. Blood counts: Hb 11 g/dL;TLC 8400/μL; DLC: 72 % neutrophils, 25 % lymphocytes,3 % monocytes; and platelet count: 6000/μL. No atypicalcells on the peripheral smear except for a few large platelets.

Is it ITP? How to Confirm the Diagnosis? History, exami-nation and a reliable review of the blood count and peripheralsmear are keystones for the diagnosis of ITP. The classicalpresentation is an acute onset of skin/mucosal bleeding in anotherwise normal child. Blood counts show isolated throm-bocytopenia and peripheral smear reveals no abnormal cellsother than large platelets. A bone marrow examination is notindicated in the majority; indications include: 1) Atypicalclinical features: Organomegaly, lymphadenopathy, bonepains or disproportionate anemia 2) Leucopenia or leukocy-tosis, particularly with lymphocytosis 3) Prior to administra-tion of steroids [16].

How to Treat This Boy? Hematologists world over are in-creasingly comfortable in avoiding pharmacological thera-pies in several patients with ITP. The American Society ofHematology 2011 evidence-based practice guidelines recom-mend that children with no bleeding or mild bleeding (definedas skin manifestations only, such as bruising and petechiae) bemanaged with observation alone regardless of platelet count.Less than 1% patients have a life threatening event in the formof intracranial hemorrhage, and 75–80 % achieve remissionwithin a period of 6 mo [16]. Studies suggest that the majorityof children experience no or mild bleeding symptoms regard-less of receiving drug therapy initially.

The treating team decided to avoid any specific therapy forincreasing platelet count in this patient. The parents werecounseled regarding the likely benign nature of the diseaseand the futility of chasing the platelet count. Advice was givento avoid trauma, contact sports and drugs affecting plateletfunctions (e.g., aspirin, ibuprofen). The skin bleeds resolvedin 10 d and the platelet count recovered spontaneously in 4 wk.

Case Scenario 2

A 5-y-old girl presented with epistaxis and bluish spots on theskin for a week. Parents felt her to be lethargic as well. Onexamination, pallor was disproportionate to bleeds, spleen tip

was palpable, apart from petechiae and purpurae. Blood counts:Hb 8 g/dL; TLC 3800/μL; DLC: 30 % neutrophils, 70 %lymphocytes and platelet count 8000/μL. The peripheral smearconfirmed leucopenia, lymphocytosis and thrombocytopenia.

How Should One Proceed? A bone marrow examination isindicated in this girl due to splenomegaly, lethargy, dispro-portionate pallor as well as leucopenia and lymphocytosis. Adiagnosis of acute leukemia was confirmed on bone marrowexamination.

Case Scenario 3

A 5-y-old,otherwise normal girl developed wide-spread skinbruises for 2 d and had two episodes of epistaxis, lasting30 min each. No organomegaly or lymphadenopathy onexamination. Blood counts: Hb: 10 g/dL; TLC: 5200/μL;DLC: 60 % neutrophils, 38 % lymphocytes, 2 % monocytes;platelet count: 8000/μL with a normal peripheral smear.

How to Manage the Above Case? A diagnosis of ITP wasmade on clinical grounds, supported by the blood counts. Inview of two episodes of ‘significant’ epistaxis, the treatingteam decided in favor of pharmacological management. Thechoices include: 1) Steroids: Authors prefer a short course ofprednisolone (4 mg/kg/d for 4 d followed by abrupt stopping),2) IVIg: Single dose, 0.8–1 g/kg. IVIg is preferred when morerapid rise in platelet count is desirable, 3) Anti-D: 75 μg/kgsingle dose in Rh-positive patients [16]. Anti-D was adminis-tered to this patient; platelet count recovered in 5 d.

Should Platelets be Transfused to SuchPatients? It is a commonerror to transfuse platelets to patients with ITP, as the autoim-mune mechanism will destroy the transfused platelets. Thispractice may only be justified in life-threatening situations(e.g., CNS bleed) along with immunosuppressive therapy.

Hemophilia

Hemophilia is an X linked disorder, observed in 1 in 5000males. Hemophilia A and B is due to deficiency of factorVIII and IX, respectively. Majority manifest by 1 y of age.The hallmark is bleeding into joints (hemarthrosis) and

Table 2 Clinical manifestations of primary hemostatic defect vs. clotting factor deficiency [15]

Clinical characteristic Primary hemostatic defect (e.g., ITP, VWD) Clotting factor deficiency (e.g., Hemophilia)

Site Skin, mucosa Soft tissues, muscles, joints

Bleeding following minor cuts Yes Not usual

Skin bleeds Petechiae or small, superficial ecchymosis Large, deep, palpable ecchymosis

Bleeding following trauma, surgery Immediate Delayed

46 Indian J Pediatr (January 2014) 81(1):42–50

intramuscular hematomas. Platelet count is normal and thecoagulogram reveals a normal PT and prolonged APTT.Diagnosis is confirmed by quantitative factor assay.

Factors are often not an option to several patients in Indiadue to cost constraints (1 vial of 250 units of factor VIII: ~Rs

2800; 1 vial of 600 units of factor IX: ~Rs 11,000). Thus,fresh frozen plasma (FFP) or cryoprecipitate are often ad-ministered as the only feasible, though, inferior alternative.FFP can be administered to patients with Hemophilia A aswell as B, whereas cryoprecipitate can only be used in

Petechiae/Purpura/Abnormal bleeding

Prolonged PT and aPTT?

NoYes

History and examination to differentiate

between primary hemostatic and

coagulation disorder (Table 2)

Screening tests

Complete blood countPeripheral smear: Platelet size/morphology

PT and aPTT

Thrombocytopenia?

DICSepsis

ITPHUSTTPAcute leukemiaAplastic anemia

Liver diseaseVitamin K deficiencyDICDeficiency of factor II, X or V

Massive transfusion

Excessive heparin

Early liver disease

Factor VII deficiency

Warfarin

Factor VIII, IX, XI deficiencyModerate to severe VWD

Child abuseHSPFactor XIII deficiencyVon Willebrand disease#

Platelet function disorder*Vascular disorders e.g., Hereditaryhemorrhagic telengiectasia,Ehler-Danlos syndrome

NoYes

PT and aPTT

NormalAbnormal

Abnormal PT and normal aPTT Normal PT and abnormal aPTT Abnormal PT and aPTT

Fig. 2 Step wise approach to a child with bleeding [15]. PTProthrombin time; aPTT Activated partial thromboplastin time;DIC Disseminated intravascular coagulation; ITP Immune throm-bocytopenia; HUS Hemolytic uremic syndrome; TTP Thrombotic

thrombocytopenic purpura; HSP Henoch-Schönleinpurpura.#Thrombocytopenia is observed in type 2B VWD. *Mild throm-bocytopenia can be present in Bernard-Soulier syndrome

Indian J Pediatr (January 2014) 81(1):42–50 47

Hemophilia A, as it does not contain factor IX [12]. In a land-mark order, in 2007, the Delhi High Court had directed the Delhistate Government to make factors available to patients withHemophilia. Under the scheme, below-poverty-line families areto be supplied factors free of cost. This was followed by a similarruling in Lucknow, Uttar Pradesh, in response to a public interestlitigation. Based on these developments, hospital authoritiesshould be convinced to make factor VIII available in the hospitalat least for emergency use. Patients should be encouraged to keepfew vials of factors at home, for on-demand use.

Case Scenario 4

A 10 kg child with Hemophilia A presents with acutehemarthrosis of right knee. What is the dose of Factor VIII orFFP or cryoprecipitate that should be administered?

The choice of product is determined by finances andavailability. To achieve a factor level of 40 U/dL on day 1,the required dose of recombinant VIII is 200 units (40units/dL×10 kg×0.5). If cost is a limitation, the dose offactor can be reduced to half. One mL of FFP will provide0.8–1 unit, and 1 unit of cryoprecipitate contains 80–110units of factor VIII. To raise the factor level by 20%, the doseof FFP and cryoprecipitate will therefore be 200 mL and 2units (40 mL), respectively. Cryoprecipitate is preferred overFFP due to lower chances of volume overload.

The corresponding dose of recombinant factor IX in a childwith Hemophilia B, who presents with similar scenario will be480 units (40×10×1.2), to raise the factor IX level by 40 U/dL.It is a common practice to round the dose to the nearest vialsize, to prevent wastage of the expensive factors. Along withthe factor replacement, analgesics, Rest, Immobilization, Cold

Fever (>38.3°C) and neutropenia (Absolute neutrophil count <500/mm3)

HIGH RISK

Intensive phase of chemotherapyClinically unstable patientAny medical co-morbidityAny focus of infectionAbsolute neutrophil count<100/mm3

Anticipated neutropenia >7d

INPATIENT IV ANTIBIOTICS

As per locally prevailing bacteriologicalprofile and antimicrobial susceptibility data

Cefoperazone/sulbactum orPiperacillin/tazobactumVancomycin + Carbapenem ifhemodynamically unstable

OUT PATIENT ANTIBIOTICS

Good oral intakeAssured follow-up

LOW RISK

Non intensive phase of chemotherapyClinically stable with no co-morbidityNo focus of infectionAbsolute neutrophil countAnticipated neutropenia <7 d

INPATIENT IV ANTIBIOTICS

Gastrointestinal intoleranceConcern for compliance orfollow-up

DefervescenceContinue IV or oralantibiotic till ANC is risingand

If fever persists >48 h,hospitalize and start IV antibiotics

Cefexime, orAmoxicillin/clavulanate, orLevofloxacillin

Adjust antimicrobials based on clinicalcourse, counts, radiology and cultures

INITIAL STABILIZATION AND INVESTIGATIONS

Take care of airway, breathing andcirculationObtain CBC, blood culture, electrolytesChest X-Ray and other cultures if indicated

500/mm3

Amikacin

100/mm3

Fig. 3 Initial management of patient with febrile neutropenia [19]

48 Indian J Pediatr (January 2014) 81(1):42–50

compression and Elevation (RICE) should be advised as well[14].

Acute Leukemia

Acute leukemia is the most common hematological malig-nancy in childhood. Acute lymphoblastic leukemia (ALL)accounts for 75 % of the acute leukemia’s in children. Com-mon presentations include persistent fever, progressive pal-lor, bleeding, bone pains and joint symptoms. Typical find-ings include pallor, lymphadenopathy, petechiae, purpurae,bony tenderness and hepatosplenomegaly. Not uncommonmanifestations include pyrexia of unknown origin, limping,back ache, etc., in absence of organomegaly. Complete bloodcount may reveal variable findings, including anemia,thrombocytopenia, normal, reduced or elevated white count,lymphocytic predominance and often (not necessary) blastsin the peripheral smear. The diagnosis is confirmed by a bonemarrow examination and immunophenotyping. As the clin-ical picture may be similar to juvenile rheumatoid arthritis, abone marrow examination is desirable prior to administrationof steroids [17].

With appropriate chemotherapy and supportive care, 70–80 % survival is achievable. The duration of treatment variesfrom 2 to 3 y. The Family physician has an important role inearly referral to Pediatric Oncology unit, encouraging thefamily to opt for treatment, shared care for administration ofchemotherapy during maintenance therapy and recognitionand initial management of febrile neutropenia. The cost oftreatment for ALL in author’s institution is approximatelyRs. 1.5 to 2.5 lakhs. Financial assistance may be possible forselected patients at several centers. A stay of the patient andthe care-takers in the vicinity of the hospital is necessary forinitial 6 mo of treatment.

Febrile Neutropenia

Primary care physicians have vital role in timely recognitionand initial management of patients with febrile neutropenia.Children receiving chemotherapy for malignancies such asacute leukemia, lymphoma and solid tumors, and those withaplastic anemia very often present with febrile neutropenia.Stabilization, immediate antibiotic administration and sup-portive care form the cornerstone of management.

Any patient receiving chemotherapy who presents withfever [single oral temperature of ≥38.3 °C (101 °F) or atemperature of ≥38.0 °C (100.4 °F) for ≥1 h] should besuspected to have febrile neutropenia. The first contact phy-sician should take active interest in managing such patients,particularly if the Oncology unit is not close by. Vitals shouldbe assessed. Blood sample should be sent for counts and if

possible, for a culture as well. First dose of antibiotics (variousoptions, one choice is Cefoperazone/sulbactum ± Amikacin)should be administered. Presumptive treatment for malaria isnot recommended [18]. Further decisions are based on countsand clinical condition (Fig. 3). The physician should nothesitate in calling the contact at the Oncology center forinputs. The formula for calculating absolute neutrophil count(ANC) is Total leucocyte count × neutrophil %; divided by100. (e.g., a patient with a TLC of 2300 and a neutrophil of15 %, will have an ANC of 2300×15/100=345).

Conflict of Interest None.

Role of Funding Source None.

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