The Relapses in Childhood Acute Lymphoplastic Leukemia Excluding L3
Condition: Leukemia, Acute
MeSH terms: Leukemia
Study type: Observational

Summary: 
      Background: acute lymphoblastic leukemia is the most common childhood cancer and relapse is
      the main reason for treatment failure in childhood acute lymphoblastic leukemia.

      The aim of this study: is to assess the relapse of childhood acute lymphoblastic leukemia in
      pediatric patients treated in the Child's Central Teaching Hospital/ Baghdad.

      Methods: A retrospective study that reviewed 521 children with newly diagnosed ALL for
      children below 15 years during the period from 1st of January 2013 to 1st of March 2020 in
      the hemato-oncology ward in the Child's Central Teaching Hospital in Baghdad, with a total
      duration of follow-up for two years post last starting treatment (till 1st of March 2022 ).
    

Detailed description: 
      Six hundred patients diagnosed with acute lymphoblastic leukemia, seventy-nine patients were
      excluded from study, nine patients died very early before starting induction, seventy
      patients referred or starting treatment in another centers.

      The medical history, laboratory data had been taken for patients including age, gender,
      residence, date of diagnosis, date of treatment, outcome of induction period and time of
      relapse, investigations at time of relapse, therapy and relapse outcome were carried out
      through chart analysis.

      The initial diagnosis of ALL was done through bone marrow aspiration morphological
      classification of blast cells was performed according to the FAB method while
      immunophenotyping not done for all patients (not available in the period from 2013 to 2016(
      227 cases not diagnosed by flowcytometry,294 cases diagnosed by flowcytometry), cytogenetic
      study not available in our country. The initial diagnostic screen (complete blood count and
      blood film, renal function test and serum electrolytes and serum uric acid, liver function
      tests, hepatitis screen, chest x ray, echo-study, computerized tomography and MRI done for
      indicated cases.

      Risk group of patients at time of intial diagnosis divided into standard risk group (age
      between 1 years and 9.9 years and initial WBC count less than50000) and high risk group (age
      less than 1 and more than 10 years and WBC count more than 50000 and T cell leukemia) .

      Patients regarded and treated as T cell leukemia either by flow cytometry or on clinical
      bases (mediastinal widening) which associated with(older age,high WBC count, lymphadenopathy,
      hepatosplenomegaly).

      The patients were treated initially with regimens modified from United Kingdom Acute
      Lymphocytic Leukemia protocols (306 patients were treated by UKALL 2003 for precursor B cell
      with modification on protocol by increasing the number of intra-thecal dose during period of
      induction therapy and 22 patients were treated by NHL/BFM 95 protocols for T cell leukemia
      and used from 1st January 2013 to 1st October 2017, and 193 patients were treated with
      modified MRC ALL 2011,the modification done by increasing number of intr-thecal dose during
      the induction period and decreasing high dose of methotrexate from 5 g/m2 to 2g/m2 , from 1st
      of October to 1st of March 2020) .

      The treatment protocols for relapsed cases were modified from MRC-UKALL -R3 protocol , the
      modification was clofarabin not available and patients were treated by intermediate R3
      protocol to adapt local limitation of supportive measures and the shortage of
      chemotherapeutic agents.

        -  Infantile leukemia was treated with same protocol and treated as high risk group.

        -  CNS positive at time of patients presentation treated according to their age and WBCs
           count .

        -  Limitation of study : cytogenetic study and MRD are not available in country at time of
           study .

        -  B.M.A was done at day eight and day fifteen after started induction and according to the
           results shifted to another protocol.

      Definition of relapse:

      An isolated BM relapse was diagnosed with 25% lymphoblast in the BM and without evidence of
      leukemia at extra medullary sites. Accordingly, isolated extramedullary relapses were those
      with the clinically-overt extramedullary manifestation of leukemia and less than 5% marrow
      infiltration. CNS relapse was diagnosed in the case of positive the unequivocal presence of
      lymphoblasts per microliter CSF or clinical signs of CNS leukemia such as facial nerve palsy,
      brain/eye involvement .

      Testicular relapse was diagnosed by clinical examination and ultrasound, the involvement of
      any other extramedullary site was confirmed histologically.in this study one case presented
      with late relapse of cervical lymph node and biopsy done that show T lymphoblastic lymphoma
      with blast cell less than 1% in B.M. In children with proven leukemia at extramedullary
      sites, a combined relapse was diagnosed with marrow involvement of lymphoblasts.

      Complete remission was defined as the absence of leukemic blasts in peripheral blood and CSF
      and less than 5% blast on bone marrow aspirate smear, together with hematopoietic
      regeneration and no evidence of extramedullary (localized) disease.

      Induction failure was defined as the failure to achieve remission after 1 month of therapy.

      Abandonment of treatment was defined as care termination by the parent/caregiver and/or if
      more than 4 weeks was exceeded with a no-show/non-attendance for a scheduled treatment by the
      patient .

      Overall survival defined as the time from date of diagnosis and or start treatment to the
      date of death.

      Time of relapse

      Based on time factor, relapses were categorized as:

        -  Very early: within 18 months of diagnosis, while on chemotherapy

        -  Early: occurred after 18 months of diagnosis and within 6 months of treatment completion

        -  Late: relapse documented more than 6 months after completion of therapy.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        A retrospective study that reviewed 521 children with newly diagnosed ALL for children
        below 15 years during the period from 1st of January 2013 to 1st of March 2020 in the
        hemato-oncology ward in the Child's Central Teaching Hospital in Baghdad, with a total
        duration of follow-up for two years post last starting treatment (till 1st of March 2022 ).