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1.
JCO Glob Oncol ; 10: e2300399, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38422460

ABSTRACT

PURPOSE: To share our clinical experience with the diagnosis and management of children with hematolymphoid malignancies presenting with epilepsia partialis continua (EPC) as a sequelae of measles infection. MATERIALS AND METHODS: In December 2022, a series of children in our hemato-oncology unit presented with focal status epilepticus with no conclusive evidence pointing toward any underlying etiology. One such child had a typical measles rash a few weeks before the onset of this focal status epilepticus. After a series of cases with a similar presentation, a clinical pattern suspicious for measles became evident. cerebrospinal fluid polymerase chain reaction was positive for measles virus with measles immunoglobin M detected in the serum. This led to the diagnosis of measles inclusion-body encephalitis in a series of children who presented with EPC over a period of 3 months. EPC is a rare manifestation of measles that is seen only in immunocompromised patients. RESULTS: Among the 18 children reported in this series, only 10 had a history of rashes. The rash was mostly transient and elicited only on retrospective history taking. Five of the 18 children who did not lose consciousness during the prolonged seizure episode survived the disease but had residual neurologic sequelae. Among the 18 children, two were unimmunized and immunization status could not be confirmed in three other children. CONCLUSION: This case series highlights the threats posed by measles infection in children with cancer who are immunosuppressed because of the underlying disease and ongoing chemotherapy. Loss of herd immunity because of declining measles immunization rates secondary to vaccine hesitancy and COVID-19 lockdown pose a greater risk of measles infection and its complications for patients with deficient immune systems.


Subject(s)
Epilepsia Partialis Continua , Exanthema , Measles , Neoplasms , Child , Humans , Retrospective Studies , Epilepsia Partialis Continua/drug therapy , Epilepsia Partialis Continua/etiology , Measles/complications , Neoplasms/complications , Disease Progression , Exanthema/complications
2.
Eur J Haematol ; 112(1): 122-136, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37706583

ABSTRACT

OBJECTIVES: Measurable residual disease (MRD) is the most relevant predictor of disease-free survival in B-cell acute lymphoblastic leukemia (B-ALL). We aimed to establish a highly sensitive flow cytometry (MFC)-based B-ALL-MRD (BMRD) assay for patients receiving anti-CD19 immunotherapy with an alternate gating approach and to document the prevalence and immunophenotype of recurrently occurring low-level mimics and confounding populations. METHODS: We standardized a 15-color highly-sensitive BMRD assay with an alternate CD19-free gating approach. The study included 137 MRD samples from 43 relapsed/refractory B-ALL patients considered for anti-CD19 immunotherapy. RESULTS: The 15-color BMRD assay with CD22/CD24/CD81/CD33-based gating approach was routinely applicable in 137 BM samples and could achieve a sensitivity of 0.0005%. MRD was detected in 29.9% (41/137) samples with 31.7% (13/41) of them showing <.01% MRD. Recurrently occurring low-level cells that showed immunophenotypic overlap with leukemic B-blasts included: (a) CD19+CD10+CD34+CD22+CD24+CD81+CD123+CD304+ plasmacytoid dendritic cells, (b) CD73bright/CD304bright/CD81bright mesenchymal stromal/stem cells (CD10+) and endothelial cells (CD34+CD24+), (c) CD22dim/CD34+/CD38dim/CD81dim/CD19-/CD10-/CD24- early lymphoid progenitor/precursor type-1 cells (ELP-1) and (d) CD22+/CD34+/CD10heterogeneous/CD38moderate/CD81moderate/CD19-/CD24- stage-0 B-cell precursors or ELP-2 cells. CONCLUSIONS: We standardized a highly sensitive 15-color BMRD assay with a non-CD19-based gating strategy for patients receiving anti-CD19 immunotherapy. We also described the immunophenotypes of recurrently occurring low-level populations that can be misinterpreted as MRD in real-world practice.


Subject(s)
Antibodies, Bispecific , Burkitt Lymphoma , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Humans , Flow Cytometry , Endothelial Cells , Antigens, CD19 , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Neoplasm, Residual/diagnosis
3.
Pediatr Blood Cancer ; 71(2): e30791, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38014874

ABSTRACT

BACKGROUND: Pediatric core binding factor acute myeloid leukemia (CBF-AML), although considered a favorable risk subtype, exhibits variable outcomes primarily driven by additional genetic abnormalities, such as KIT mutations. PROCEDURE: In this study, we examined the prognostic impact of KIT mutations in 130 pediatric patients with CBF-AML, treated uniformly at a single center over 4 years (2017-2021). KIT mutations were detected via next-generation sequencing using a myeloid panel comprising 52 genes for most patients. RESULTS: Our findings revealed that KIT mutations were present in 31% of CBF-AML cases. Exon 17 KIT mutation was most commonly (72%) seen with notable occurrences at the D816 and N822 residue in 48% and 39% of cases, respectively. The 3-year cumulative incidence of relapse (CIR) and overall survival (OS) for patients with exon 17 KIT mutation were 36% and 40%, respectively, and was significantly worse in comparison to other site KIT mutations (3-year CIR: 11%; OS: 64%) and without KIT mutation (3-year CIR: 13%; OS:71%). Notably, the prognostic impact of KIT mutations was prominent in patients with RUNX1::RUNX1T1, but not in those with CBFB::MYH11 fusion. Additionally, a high KIT variant-allele frequency (VAF) (>33%) predicted for a higher disease relapse; 3-year CIR of 40% for VAF greater than 33% versus 7% for VAF less than 33%. When adjusted for site of KIT mutation and end-of-induction measurable residual disease, VAF greater than 33% correlated with poor OS (hazard ratio [HR]: 4.4 [95% CI: 1.2-17.2], p = .034). CONCLUSION: Exon 17 KIT mutations serve as an important predictor of relapse in RUNX1::RUNX1T1 pediatric AML. In addition, a high KIT VAF may predict poor outcomes in these patients. These results emphasize the need to incorporate KIT mutational analysis into risk stratification for pediatric CBF-AML.


Subject(s)
Core Binding Factor Alpha 2 Subunit , Leukemia, Myeloid, Acute , Humans , Child , Core Binding Factor Alpha 2 Subunit/genetics , Proto-Oncogene Proteins c-kit/genetics , Leukemia, Myeloid, Acute/therapy , Mutation , Prognosis , Exons/genetics , Recurrence , RUNX1 Translocation Partner 1 Protein/genetics
4.
Br J Haematol ; 204(4): 1249-1261, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38098201

ABSTRACT

Tyrosine kinase inhibitors (TKIs) have drastically improved the outcomes of pCML (paediatric CML) but data on long-term off-target toxicities of TKIs in children are scarce. In this single-centre, retrospective cum prospective study of pCML in chronic phase, we report our experience of treating 173 children with imatinib and following them for long-term toxicities. Mean (SD) time to attain CHR, CCyR and MMR were 3.05 (2.1), 10.6 (8.4) and 43.4 (31.8) months respectively. DMR was not attained in 59 (34%) patients at last follow-up. Ten patients were switched to second-generation TKIs (2G-TKIs; nilotinib = 1/dasatinib = 9) due to poor/loss in response, of which seven had kinase domain mutations. Three patients progressed to the blastic phase. At a median follow-up of 84 (3-261) months, the 5-year EFS and OS for the entire cohort were 96.9% (95% CI: 93.4-100) and 98.7% (95% CI: 96.9-100) respectively. Screening for long-term toxicities revealed low bone density and hypovitaminosis D in 70% and 80% respectively. Other late effects included short stature (27%), delayed puberty (15%), poor sperm quality (43%) and miscellaneous endocrinopathies (8%). Children younger than 5 years at diagnosis were more susceptible to growth and endocrine toxicities (p = 0.009). Regular monitoring for long-term toxicities, timely intervention and trial of discontinuation whenever feasible are likely to improve the long-term outlook of pCML.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Child , Humans , Male , Dasatinib , Follow-Up Studies , Hospitals , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Retrospective Studies , Semen , Treatment Outcome , Child, Preschool
5.
Am J Blood Res ; 13(5): 162-167, 2023.
Article in English | MEDLINE | ID: mdl-38023415

ABSTRACT

Central nervous system (CNS) involvement in Hodgkin lymphoma (HL) is an extremely rare presentation with dismal outcomes according to reported literature. An 8-year-old girl presented to us with complaints of on-off fever, right cervical swelling and bilateral ptosis. Positron emission tomography (PET) showed intracranial extra-axial soft tissue masses in right infero-lateral temporal lobe, sella and bilateral parasellar region along with cervical, mediastinal, axillary, abdominal and inguino-pelvic nodes, liver lesions and extensive marrow lesions involving the axial and appendicular skeleton. Histopathology of the cervical lymph node revealed a diagnosis of classical Hodgkin lymphoma. Child received 2 cycles of OEPA and 4 cycles of COPP followed by radiotherapy to bulky cervical lymph nodes and intracranial lesion. The child has been disease-free for 44 months with no neurological sequalae. Intracranial spread is rare in Hodgkin lymphoma and is associated with inferior outcomes. Due to its rarity, there are no specific treatment guidelines for this entity. The choice of ideal chemotherapeutic agents and role of whole-brain radiotherapy needs further evaluation.

6.
Leuk Lymphoma ; 64(12): 1971-1980, 2023 12.
Article in English | MEDLINE | ID: mdl-37565568

ABSTRACT

Methotrexate-induced neurotoxicity is a well-defined side-effect of high-dose and intrathecal methotrexate with characteristic clinico-radiological findings and transient nature. Our experience in managing this entity in children with acute lymphoblastic leukemia(ALL) is reported here. All children with de novo ALLregistered from January 2016 through December 2021 who developed methotrexate-induced neurotoxicity were included. Of children with ALL treated during the study period, thirty-three experienced methotrexate induced neurotoxicity with an incidence of 1.25%. Stroke-like symptoms(36.36%; 12/33) were the most common clinical manifestation followed by seizures(30.3%, 10/33). Twenty-three patients had radiological features consistent with methotrexate-induced leukoencephalopathy. With emerging evidence, thirty-one patients were re-challenged with methotrexate (IV/IT), of whom 4 patients had recurrence of symptoms. No long-term neurological sequalae were noted in our cohort, despite rechallenging. Therefore in our study, methotrexate induced neurotoxicity is a self-limiting toxicity and methotrexate can be re-challenged safely without compromising theintensity of CNS-directed therapy.


Subject(s)
Leukoencephalopathies , Methotrexate , Neurotoxicity Syndromes , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Follow-Up Studies , Leukoencephalopathies/chemically induced , Leukoencephalopathies/complications , Leukoencephalopathies/diagnosis , Methotrexate/adverse effects , Neurotoxicity Syndromes/diagnosis , Neurotoxicity Syndromes/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Radiography
7.
Pediatr Blood Cancer ; : e30547, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37409841

ABSTRACT

Sepsis-related mortality continues to be a major concern while treating pediatric cancer patients, more so with the rise in the incidence of multidrug-resistant organisms (MDRO). In this retrospective study conducted between January 2021 and December 2022 at a tertiary cancer center in India, granulocyte transfusion was offered in addition to standard antimicrobial therapy to 64 children with hematolymphoid malignancy who developed 75 episodes of severe sepsis following intensive chemotherapy. Forty-four (83%) of 53 blood culture proven sepsis was caused by MDROs. Thirty-seven (70%) patients with blood culture proven sepsis cleared the organism after granulocyte transfusion. Thirty-day mortality was 25% for the entire study cohort and 32% for patients with MDRO sepsis.

8.
Ann Hematol ; 102(10): 2835-2844, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37479890

ABSTRACT

The outlook of relapsed ALL in low- and middle-income countries (LMICs) is dismal due to high treatment-related toxicities and inadequate resources. We report our experience of using a locally adapted mitoxantrone-based protocol for non-high risk (HR) relapsed B-ALL (rALL). A retrospective cum prospective study of standard and intermediate risk (SR and IR) rALL patients treated on TMH rALL-18 protocol (adapted from COG/UKALLR3/Int-Re-ALL protocols) between November 2018 and January 2021 was analyzed. The protocol comprising of 7 blocks of multi-agent chemotherapy including mitoxantrone in induction followed by local irradiation and maintenance, underwent serial modifications based on our experience with initial patients. Eighty-two patients (SR rALL, 3; IR rALL, 79) were treated on TMH rALL-18 protocol. Of 321 grade 3/4 reported toxicities, around 43% (138 toxicities) were noted during induction. Induction chemotherapy was outpatient-based; however, 68 patients (82.9%) required supportive care admissions. Twelve out of 19 patients with gram negative bacilli sepsis (included 7 MDRO) died during reinduction. Five remission deaths were seen during block 3 after which cytarabine was dose reduced (3 g to 2 g/m2). Post-reinduction minimal residual disease was negative in 54 (80.6%) out of 67 evaluable patients. At a median follow-up of 24 months (95% CI 22-27), the estimated 2-year event-free and overall survival of the entire cohort was 58% (95% CI 48.1-69.9) and 60.3% (95% CI 50.5-72). Until the time, targeted therapies are freely accessible in LMICs, strengthening supportive care as well as local adaptation of protocols that strike a fine balance between efficacy and tolerability are mandated.


Subject(s)
Bacteremia , Mitoxantrone , Humans , Child , Prospective Studies , Retrospective Studies , Hospitals , India/epidemiology
9.
Indian J Pediatr ; 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37380920

ABSTRACT

OBJECTIVES: Outcomes of childhood acute promyelocytic leukemia (APL) have exceeded 90% in the era of differentiating agents. In resource-limited settings, early mortality secondary to coagulopathy remains a significant challenge. Differentiation syndrome is a unique complication of APL therapy that requires a high degree of suspicion for timely initiation of therapy. METHODS: A retrospective study of children ≤15 y of age with APL diagnosed between January-2013 and June-2019 treated at a tertiary cancer centre was conducted. Patients with a total leukocyte count ≥10,000/µL were risk stratified as high-risk. Treatment included differentiating agents, all-trans retinoic acid and arsenic trioxide along with chemotherapy. Baseline demographics, clinical complications and outcomes were analysed. RESULTS: Out of 90 patients treated, 48 (53%) had high-risk APL and 25 (28%) presented with significant bleeding manifestations. Response to therapy was excellent with 96% of evaluable patients achieving molecular remission by the end of consolidation phase. Differentiation syndrome occurred in 23 (25%) patients of which two expired. Early mortality rate was 5.5% and was due to severe hemorrhage most often at the time of presentation. The 3-y overall survival of the entire cohort was 91% (95% CI: 85-97%). Two of 4 patients with relapse of disease could be salvaged with only differentiating agents followed by autologous transplantation. CONCLUSIONS: Long-term outcomes of Indian children with APL are excellent. Timely management of coagulopathy and prompt initiation of differentiating agents along with appropriate cytoreductive measures is critical. Efforts to build academic-community partnerships to ensure timely diagnosis and emergency care in order to reduce early mortality are needed.

10.
Pediatr Blood Cancer ; 70(2): e30096, 2023 02.
Article in English | MEDLINE | ID: mdl-36401555

ABSTRACT

BACKGROUND AND AIMS: Thrombotic events (TEs) have been extensively studied in adult cancer patients, but data in children are limited. We prospectively analyzed pediatric cancer-associated thrombosis (PCAT) in children with malignancies. METHODS: Children below 15 years of age with confirmed malignancies, treated at a large tertiary cancer center in India from July 2015 to March 2020 developing any TE were eligible. A standardized approach for detection and management was followed. Data were collected after informed consent. RESULTS: Of 6132 eligible children, 150 (2.44%) had 152 TEs, with median age 8.5 years and male:female of 1.83:1. Most TEs occurred on chemotherapy: 111 (74.0%). The most common site was central nervous system (CNS) 59 (39.3%), followed by upper-limb venous system 37 (24.7%). Hemato-lymphoid (HL) malignancies were more prone to PCAT than solid tumors (ST) (incidence 3.23% vs. 1.58%; odds ratio [OR] = 2.06, 95% confidence interval [CI] [1.36-2.88]; p < .001). Malignancies associated with PCAT were acute lymphoblastic leukemia (ALL) 2.94%, acute myeloid leukemia (AML) 6.66%, and non-Hodgkin lymphomas 5.35%. Response imaging done in 106 (70.7%) children showed complete to partial resolution in almost 90% children. Death was attributable to TE in seven (4.66%) children. Age above 10 years (OR 2.33, 95% CI [1.59-3.41]; p < .001), AML (OR 4.62, 95% CI [1.98-10.74]; p = .0062), and non-Hodgkin lymphoma (OR 4.01, 95% CI [1.15-14.04]; p = .029) were significantly associated with TEs. In ALL, age more than 10 years (OR 1.86, 95% CI [1.06-3.24]; p < .03), T-ALL (OR 3.32, 95% CI [1.69-6.54]; p = .001), and intermediate-risk group (OR 4.97, 95% CI [1.12-22.02]; p = .035) were significantly associated with thrombosis. The 2-year event-free survival (EFS) for HL malignancies with PCAT was 55.3% versus 72.1% in those without PCAT (p = .05), overall survival (OS) being 84.6% versus 80.0% (p = .32). CONCLUSION: Incidence of PCAT was 2.4%, and occurred predominantly in older children with hematolymphoid malignancies early in treatment. Most resolved completely with low molecular weight heparin (LMWH) and mortality was low. In hematolymphoid malignancies, PCAT reduce EFS, highlighting the need for prevention.


Subject(s)
Leukemia, Myeloid, Acute , Lymphoma, Non-Hodgkin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Thrombosis , Child , Adult , Humans , Male , Female , Heparin, Low-Molecular-Weight , Tertiary Healthcare , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Leukemia, Myeloid, Acute/complications
11.
J Pediatr Hematol Oncol ; 45(4): 213-215, 2023 05 01.
Article in English | MEDLINE | ID: mdl-35973102

ABSTRACT

In children with underlying Human Immunodeficiency virus infection and AIDS, hematolymphoid cancers, especially non-hodgkin lymphomas are common. Plasmablastic lymphoma is one such non-hodgkin lymphomas arising from the head and neck region (especially sinonasal) but extremely rare. We describe the clinical course in a 4-year-old boy who presented with a solitary bony swelling of the right knee joint, which on diagnostic work-up turned out to be plasmablastic lymphoma. With combination chemotherapy, intrathecal chemotherapy, and early institution ofHighly active anti-retroviral therapy, the child continues to be in remission.


Subject(s)
HIV Infections , Lymphoma, AIDS-Related , Lymphoma, Non-Hodgkin , Plasmablastic Lymphoma , Male , Humans , Child, Preschool , Plasmablastic Lymphoma/diagnosis , Plasmablastic Lymphoma/pathology , HIV , Peritoneum/pathology , HIV Infections/complications , HIV Infections/drug therapy , Lymphoma, Non-Hodgkin/pathology , Lymphoma, AIDS-Related/pathology
12.
Cancer Chemother Pharmacol ; 90(6): 445-453, 2022 12.
Article in English | MEDLINE | ID: mdl-36251032

ABSTRACT

AIMS: L-asparaginase is an essential medicine for childhood ALL. The quality of generic L-asparaginase available in India is a matter of concern. We compared four commonly used generic formulations of L-asparaginase in India. MATERIALS AND METHODS: We conducted a prospective, open-label, randomised trial of four generic formulations of asparaginase for the treatment of patients with newly diagnosed intermediate-risk B-ALL. Patients were randomly assigned in a 1:1:1:1 ratio to receive generic asparaginase at a dose of at 10,000 IU/m 2 on days 9, 12, 15, and 18 of a 35-day cycle (Induction treatment). The primary end points were to determine the difference in the asparaginase activity and asparagine depletion. Historical patients who received L-asparaginase Medac (innovator) served as controls. RESULTS: A total of 48 patients underwent randomization; 12 patients each in the four arms. Failure to achieve predefined activity threshold of 100 IU/L was observed in 9/40 samples of Generic A (22·5%), 23/40 of Generic B (57·5%), and 43/44 (98%) each of Generic C and D. All 27 samples from seven historical patients who were administered Medac had activity > 100 IU/L. The average activity was significantly higher for Genericm A, 154 (70·3, 285·4) IU/L followed by Generic B 84·5(44·2, 289·1) IU/L, Generic C 45(14·4, 58·4) IU/L, and Generic D 20·4(13, 35) IU/L. Only 6 patients had asparaginase activity > 100 IU/L on each of the four occasions (Generic A = 5; Generic B = 1), and none of them developed Anti-Asparaginase Antibodies (AAA). On the other hand, AAA was observed in 12/36 patients who had at least one level < 100 IU/L (P < 0·05): Generic A 3/5, Generic B = 3/9, Generic D (4/11), and Generic C (5/11). CONCLUSION: Generic A and B had better trough asparaginase activity compared to Generic D and C. Overall, generic formulations had lower asparaginase activity which raises serious clinical concerns regarding their quality. Until strict regulatory enforcement improves the quality of these generics, dose adaptive approaches coupled with therapeutic drug monitoring need to be considered.


Subject(s)
Antineoplastic Agents , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Asparaginase/therapeutic use , Precursor Cells, B-Lymphoid , Prospective Studies , Antineoplastic Agents/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Drugs, Generic/therapeutic use , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antibodies
13.
Implement Sci Commun ; 3(1): 62, 2022 Jun 11.
Article in English | MEDLINE | ID: mdl-35690878

ABSTRACT

BACKGROUND: The recent implementation of novel therapies has accelerated progress in pediatric cancer care. Despite the significantly poorer survival of patients in low- and middle-income countries (LMICs), administation complexities and other significant resource barriers have limited the translation of these novel therapies in these regions. This study aims to develop a model that can be used to support the implementation of novel therapies, such as blinatumomab (bispecific antibody therapy for B-cell acute lymphoblastic leukemia [B-ALL]) in LMIC centers, with the long-term goal of developing an implementation framework for similar future efforts. METHODS: In this study, mixed methods will be applied to understand the key contextual considerations that can be accounted for through a training program and prospectively designed implementation activities. The Consolidated Framework for Implementation Research will guide the activities related to implementation evaluation in parallel with a drug donation program. A multidisciplinary research team comprising high- and low-middle income healthcare professionals, industry, and implementation scientists has been assembled with the common goal of improving safe access to blinatumomab. To assess the factors affecting blinatumomab administration, semi-structured interviews with diverse collaborators and quantitative assessments of organizational characteristics will be conducted, together with quantitative and qualitative assessments of feasibility, acceptability, appropriateness, and cost of blinatumomab implementation. A quantitative assessment of stakeholder perceptions of different implementation strategies used as part of the multifaceted approach will also be performed. Finally, we will examine the key domains and processes used and construct the implementation roadmap for translation of novel therapies. DISCUSSION: This study will rigorously develop an implementation roadmap for translation of novel therapies in low-resource settings. The knowledge gained in the formative assessment will reveal the priority areas and key implementation strategies. Thereby, the resultant roadmap will facilitate future scale-out strategies for novel therapies in LMICs, thus increasing access, building capacity for management, and ultimately improving the care for children in LMICs.

14.
Childs Nerv Syst ; 38(9): 1689-1698, 2022 09.
Article in English | MEDLINE | ID: mdl-35614149

ABSTRACT

BACKGROUND AND AIM: Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome characterized by a neurotoxic state with vasogenic edema. We studied the clinical profile, predisposing factors, imaging features, and outcome of PRES in children receiving treatment for hematolymphoid malignancies. METHODS: Retrospective analysis of the clinical data and radiological features of patients with PRES diagnosed between June 2014 and December 2019. RESULTS: Fifty-two patients (boy: girl = 3:1) were diagnosed with PRES during the study period with a median age of 11 (range:1-15) years. Primary diagnoses were acute leukemias (n = 42), non-Hodgkin lymphoma (n = 8), Hodgkin lymphoma (n = 1), and Langerhan's cell histiocytosis (n = 1). Most common presenting symptoms were seizures (n = 52), altered sensorium (n = 42), headache (n = 39), and visual disturbances (n = 8). Hypertension at time of diagnosis was noted in 50 (96%) patients. Classic hyper-intense lesions on FLAIR and diffusion weighed (DW) images were noted in parieto-occipital region in 39 patients (75%). Central PRES involving basal ganglia was seen in 3 (6%) patients. A subsequent neuro-imaging was done in 18 patients (MRI: 13; CT: 5) at a median interval of 16.2 weeks. Neurological sequelae were observed in 10 (19%) patients, whereas 1 succumbed due to PRES. CONCLUSIONS: PRES is an important clinico-radiological syndrome in patients undergoing chemotherapy for hematological malignancies. High index of suspicion, early diffusion-weighted images on MRI in children with classic symptoms help in early diagnosis. A small minority of patients may develop long-term sequelae.


Subject(s)
Neoplasms , Posterior Leukoencephalopathy Syndrome , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Magnetic Resonance Imaging/methods , Male , Neoplasms/complications , Posterior Leukoencephalopathy Syndrome/complications , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , Retrospective Studies , Seizures/complications
15.
Pediatr Blood Cancer ; 69(7): e29728, 2022 07.
Article in English | MEDLINE | ID: mdl-35441780

ABSTRACT

BACKGROUND: The management of malnutrition in children with cancer remains a challenge in low-middle-income countries (LMICs). We describe our pediatric oncology nutrition program and its impact over the past decade. METHODS: We evaluated the impact of our nutrition program in accordance with the International Society of Paediatric Oncology-Paediatric Oncology in Developing Countries (SIOP PODC) Nutritional Program Evaluation in the areas of service delivery (number served, increments in delivery, number of trained care providers), patients at-risk (proportion identified with malnutrition at diagnosis/follow-up), and efficiency of nutritional interventions (proportion assessed, proportion achieved healthy weight, clinicians trained). We analyzed available data for trends between 2009 and 2020, and comparisons were made using the Fisher t test. This study was approved by our institutional ethics committee. RESULTS: From 2010 to 2020, 17 749 children treated at our center were beneficiaries of the nutritional program, including assessment and intervention. During this period, trained pediatric nutritionists increased from 2 to 8; SIOP PODC level from 2 to 3-4, and nutrition budget increased 15-fold. At diagnosis (n = 5618) and six-month follow-up (n = 2674), 59.6% and 51.2% children were undernourished, 34.8% and 43% well nourished, and 4.7% and 5.7% overnourished. From 2016 onward, fewer children were undernourished at follow-up-69.5% (2016), 60% (2018), 54% (2019), and 55% (2020, P < 0.001). The program helped train over 500 clinicians in nutrition. CONCLUSIONS: Improved financial support and capacity building have helped build and sustain an effective nutrition program. Priority areas include implementation of best practices, early nutritional intervention, continued education, and locally relevant research.


Subject(s)
Neoplasms , Nutrition Therapy , Child , Developing Countries , Humans , Medical Oncology/education , Neoplasms/therapy , Nutritional Status
17.
J Pediatr Hematol Oncol ; 44(3): e760-e764, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35129150

ABSTRACT

Clinicopathologic profile and outcome of 15 children (15 years or above) with diffuse large B-cell lymphoma treated with MCP-842 protocol are reported. Eleven of 15 presented with advanced (stage-III/IV) disease. Post-2 cycles of chemotherapy, complete metabolic and morphologic response was documented in 10 (66%) and rest 5 (33%) with partial response achieved complete metabolic remission by end of treatment. At a median follow-up of 44 months (range: 16 to 79 mo), the 3-year event-free survival and overall-survival were 77.1%±11.7% and 85.7%±9.4%, respectively. Though majority of our patients had advanced disease, outcome on MCP-842 protocol was satisfactory.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Cyclophosphamide , Humans , India/epidemiology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Remission Induction , Treatment Outcome , Vincristine
18.
Pediatr Hematol Oncol ; 39(5): 427-440, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35179438

ABSTRACT

Pediatric B-cell lymphoblastic lymphoma (LBL) is a rare entity, and appropriate treatment for pediatric B-cell LBL is not well defined. While intensive ALL type regimens achieve long term survival of 90% across Western co-operative group trials, published data from Asian studies on long term outcomes are scarce. We retrospectively analyzed the data of pediatric B-cell LBL patients treated between January 2010 and December 2017 on a uniform protocol (modified BFM 90). Kaplan-Meier method was used to estimate the survival and Cox regression models to identify prognostic factors. Of 21 patients who received treatment on the modified BFM-90 protocol, 17(81%) were alive in remission, 3(14%) had relapse, and 1(4%) had treatment-related mortality (TRM) while in remission. Two of 3 relapsed patients subsequently expired. With a median follow-up of 66 months (range 6-114), 5-year event free survival (EFS) and overall survival (OS) were 80% (95% CI:71-89%) and 91% (95% CI:85-97%), respectively. While delayed presentation from symptom onset (p=0.030), and partial response at early (D35) interim assessment (p=0.025) had inferior EFS, patients with elevated baseline LDH had a worse OS (p=0.037). Outcomes of pediatric B-cell LBL patients treated on a modified BFM-90 protocol at a single center in India were excellent. In our study, higher disease burden manifested by elevated baseline LDH and delayed presentation (≥3months) and partial interim response portend poorer survival.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2005725.


Subject(s)
Lymphoma, B-Cell , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Disease-Free Survival , Humans , India , Lymphoma, B-Cell/drug therapy , Neoplasm Recurrence, Local/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prognosis , Retrospective Studies , Treatment Outcome
19.
Trials ; 23(1): 102, 2022 Jan 31.
Article in English | MEDLINE | ID: mdl-35101099

ABSTRACT

BACKGROUND: In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protocol for uniform risk-stratified management of first presentation ALL based on cytogenetics and minimal residual disease levels (MRD). A multicentre randomised clinical trial opened in 2016 (ICiCLe-ALL-14) and examines the benefit of randomised interventions to decrease toxicity and improve outcomes. METHODS: Patients 1-18 years with newly diagnosed ALL are categorised into four risk groups based on presentation features, tumour genetics and treatment response. Standard risk includes young (< 10 years) B cell precursor ALL (BCP-ALL) patients with low presentation leucocyte count (< 50 × 109/L) and no high-risk features. Intermediate risk includes BCP-ALL patients with no high-risk features but are older and have high presentation leucocyte counts and/or bulky disease. High risk includes BCP-ALL patients with any high-risk feature, including high-risk genetics, central nervous system leukaemia, poor prednisolone response at treatment day 8 and high MRD (≥ 0·01%) at the end of induction. Patients with T-lineage ALL constitute the fourth risk group. All patients receive four intensive treatment blocks (induction, consolidation, interim maintenance, delayed intensification) followed by 96 weeks of maintenance. Treatment intensity varies by risk group. Clinical data management is based on a web-based remote data capture system. The first randomisation examines the toxicity impact of a shorter induction schedule of prednisolone (3 vs 5 weeks) in young non-high-risk BCP-ALL. The second randomisation examines the survival benefit of substituting doxorubicin with mitoxantrone in delayed intensification for all patients. Primary outcome measures include event-free survival (overall, by risk groups), sepsis rates in induction (first randomisation) and event-free survival rates following second randomisation. DISCUSSION: ICiCLe-ALL-14 is the first multicentre randomised childhood cancer clinical trial in India. The pre-trial phase allowed standardisation of risk-stratification diagnostics and established the feasibility of collaborative practice, uniform treatment, patient enrolment and data capture. Pre-trial observations confirm the impact of risk-stratified therapy in reducing treatment-related deaths and costs. Uniform practice across centres allows patients to access care locally, potentially decreasing financial hardship and dislocation. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI) CTRI/2015/12/006434 . Registered on 11 December 2015.


Subject(s)
Neoplasm Recurrence, Local , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Multicenter Studies as Topic , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prospective Studies , Randomized Controlled Trials as Topic , Treatment Outcome
20.
J Pediatr Hematol Oncol ; 44(1): e233-e236, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34654755

ABSTRACT

Solitary bone plasmacytoma is an extremely rare entity and is characterized by localized proliferation of monoclonal plasma cells. Plasmacytomas are extremely rare in the pediatric population. The median age at diagnosis is usually the fifth or sixth decade, with axial skeleton being more commonly involved than appendicular. We hereby, report the case of a 13-year-old boy with solitary bone plasmacytoma of the right humerus. Though extremely rare in the pediatric age group, plasmacytomas may be considered as one of the remote differentials in children presenting with solitary bone tumors.


Subject(s)
Bone Neoplasms , Humeral Fractures , Plasmacytoma , Adolescent , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Bone Neoplasms/therapy , Humans , Humeral Fractures/metabolism , Humeral Fractures/pathology , Humeral Fractures/therapy , Male , Plasmacytoma/metabolism , Plasmacytoma/pathology , Plasmacytoma/therapy
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