#52: Clinical Features and Management of Pediatric Patients Presenting with New Onset Acute Leukemia and Concomitant COVID-19

Abstract Background Infections represent a significant cause of morbidity and mortality in pediatric patients undergoing treatment for hematologic malignancies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a worldwide pandemic of coronavirus disease 2019 (COVID-19) and pediatric patients with cancer appear to be at higher risk of severe disease than reported in the general pediatric population. Data are limited on the optimal management of children infected with SARS-CoV-2 and a new diagnosis of leukemia. The objective of this study was to describe our experience of six children who presented with a new diagnosis of acute leukemia and concurrent COVID-19. Methods The study was IRB approved and children were enrolled following informed consent and assent as appropriate for age. The clinical presentations, serologic responses, treatments, and outcomes of patients who presented with acute leukemia and concurrent SARS-CoV-2 infection were abstracted. Residual blood was tested by ELISA for quantitative IgG to the SARS-CoV-2 spike protein receptor binding domain (RBD). Results From March 1, 2020 to Dec 31, 2020, 6 patients were identified with a new diagnosis of acute leukemia and SARS-CoV-2 infection including 3 with acute myeloid leukemia (AML) and 3 with acute lymphoblastic leukemia (ALL). The median age of our cohort was 9 years old (range 1 to 19 years old), 5 of 6 were male, and 4 of 6 patients were Hispanic. All 6 patients presented with symptoms that could be attributed to COVID-19 or acute leukemia, with fever being the most common. All 3 of the AML patients presented with hyperleukocytosis (white blood cell count > 50 x 109/L) and required oxygen therapy and intensive care. At the time of presentation, all patients with specimens available (n=5) had IgG antibodies to SARS-CoV-2 RBD. All patients received COVID-19 directed therapy, with remdesivir (n=5) and convalescent plasma (n=5) being the most common. Chemotherapy was modified or delayed in 5 of the 6 patients. The patient who received standard AML chemotherapy without awaiting COVID-19 directed treatment had delayed serologic response, delayed viral clearance from the nasopharynx, protracted respiratory failure, and ultimately died. For patients with a 12-week follow-up (n=5), 2 patients with AML had died, and the ALL patients were in remission and continuing their leukemia treatment. Conclusion COVID-19 may present concurrently in children with new onset leukemia resulting in severe morbidity and mortality. Our experience adds to growing evidence that children with AML and SARS-CoV-2 infection are at risk for severe COVID-19. Screening for SARS-CoV-2 infection with subsequent delay in chemotherapy and administration of COVID-19 directed therapies should be considered for pediatric patients with newly diagnosed acute leukemia and COVID-19.

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GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia

Blood Advances ◽

10.1182/bloodadvances.2018030171 ◽

2019 ◽

Vol 3 (9) ◽

pp. 1441-1449 ◽

Cited By ~ 3

Author(s):

Rohtesh S. Mehta ◽

Shernan G. Holtan ◽

Tao Wang ◽

Michael T. Hemmer ◽

Stephen R. Spellman ◽

...

Keyword(s):

Multivariate Analysis ◽

Acute Leukemia ◽

Pediatric Patients ◽

Hematopoietic Cell Transplantation ◽

Lymphoblastic Leukemia ◽

Chronic Gvhd ◽

Cox Proportional Hazards ◽

Relapse Free Survival ◽

Free Survival ◽

Grade Iii

Abstract We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy–requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen–mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation–based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.

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Investigation of donor KIR content and matching in children undergoing hematopoietic cell transplantation for acute leukemia

Blood Advances ◽

10.1182/bloodadvances.2019001284 ◽

2020 ◽

Vol 4 (7) ◽

pp. 1350-1356 ◽

Cited By ~ 2

Author(s):

Michael R. Verneris ◽

Jeffrey S. Miller ◽

Katherine C. Hsu ◽

Tao Wang ◽

Jennifer A. Sees ◽

...

Keyword(s):

Acute Leukemia ◽

Hematopoietic Cell Transplantation ◽

Cox Regression ◽

Pediatric Population ◽

Lymphoblastic Leukemia ◽

Disease Free Survival ◽

Allogeneic Transplantation ◽

Unrelated Donor ◽

Entire Cohort

Abstract Multiple models of donor killer immunoglobulin receptor (KIR) alloreactivity or KIR genotype have been reported to be protective against leukemia relapse after allogeneic transplantation. However, few studies have addressed this topic in the pediatric population. Here, we assessed the outcomes of allogeneic transplantation in children with acute lymphoblastic leukemia (ALL; n = 372) or acute myeloid leukemia (AML; n = 344) who received unrelated donor (URD) transplantation and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2005 to 2016. As expected in this pediatric population, most patients underwent myeloablative conditioning while in remission and with bone marrow as a stem cell source. We tested KIR ligand mismatch, KIR gene content (centromeric [Cen] B), KIR2DS1 mismatching, and Cen B/telomeric A using Cox regression models and found that none were significantly associated with either relapse or disease-free survival when considering the entire cohort of patients (ALL and AML), AML, or ALL separately. Moreover, there was no significant association with outcomes in the in vivo T-cell–depleted (ie, serotherapy) cohort. This study, which is the largest analysis of donor KIR in the pediatric acute leukemia population, does not support the use of KIR in the selection of URDs for children undergoing T-replete transplantation.

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Submental intubation in pediatric maxillofacial surgery: report of 2 cases

Colombian Journal of Anesthesiology ◽

10.1097/cj9.0000000000000137 ◽

1969 ◽

Vol 48 (2) ◽

pp. 91-95

Author(s):

Vanessa Alejandri-Gamboa ◽

Pedro J. Téllez-Rodríguez ◽

María C.R. López-Fernández ◽

Abel Sanjuan-Martínez ◽

Lina Sarmiento

Keyword(s):

Surgical Procedures ◽

Current Literature ◽

Pediatric Patients ◽

Pediatric Population ◽

Nasotracheal Intubation ◽

Maxillofacial Surgery ◽

Orotracheal Intubation ◽

Morbidity And Mortality ◽

Submental Intubation ◽

Review Current

Submental intubation (SMI) is useful in surgical procedures where nasotracheal intubation is contraindicated and orotracheal intubation is not ideal, making it an alternative to tracheostomy since it is performed in less time, with less morbidity and mortality, minimal postoperatory care, as well as an aesthetically acceptable scar. We present 2 cases of pediatric patients with a successful SMI. In addition, we briefly review current literature regarding pediatric population.

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Open-Label Bendamustine for Pediatric Patients with Relapsed or Refractory Acute Leukemia: Safety and Efficacy Outcomes,

Blood ◽

10.1182/blood.v118.21.3602.3602 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3602-3602 ◽

Cited By ~ 1

Author(s):

Christopher Fraser ◽

Patrick A. Brown ◽

Gail C. Megason ◽

Hyo Seop Ahn ◽

Bin Cho ◽

...

Keyword(s):

Acute Leukemia ◽

Stable Disease ◽

Pediatric Patients ◽

Lymphoblastic Leukemia ◽

Phase 1 ◽

Cell Transplant ◽

Phase 2 ◽

Platelet Recovery ◽

Duration Of Response ◽

Grade 3

Abstract Abstract 3602 Background: Acute leukemias, consisting of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), are the most common form of childhood cancers. New treatments are needed for patients whose disease progresses or recurs following established therapies. Bendamustine is an alkylating agent that has demonstrated activity in adults with chronic lymphoblastic leukemia and rituximab-refractory non-Hodgkin lymphoma (NHL). Bendamustine has antileukemic activity in adults with AML and myelodysplastic syndrome; however, there are few data regarding bendamustine in children or in childhood acute leukemia specifically. This study is a single-arm, phase 1/2 dose-escalating trial to determine the recommended phase 2 dose (RP2D), schedule, pharmacokinetics, and safety profile of bendamustine in pediatric patients with relapsed and refractory acute leukemia. Methods: Subjects were children aged 1–20 years with relapsed or refractory ALL or AML and without the opportunity for curative therapy. Acute toxic effects of prior therapy (ended ≥2 weeks prior to first dose of study drug) had resolved to grade 2 or less. Bendamustine was infused IV over 60 minutes on days 1 and 2 of each 21-day cycle, with delays allowed up to 2 weeks for neutrophil and platelet recovery. The starting dose was 90 mg/m2/dose with planned escalation to 120 and 150 mg/m2 in cohorts of 3. The dose of 150 mg/m2 was to be implemented only if 120 mg/m2 was safe, but produced subtherapeutic plasma levels compared with data from adults. In phase 2, patients were enrolled at the RP2D in phase 1. Patients were followed until disease progression, withdrawal due to safety or other reasons, loss to follow-up, or a maximum of 12 cycles. After the end of treatment, patients were evaluated every 3 months for 12 months after the last dose, or until progression, death, or start of new cancer treatment. Overall response rate was assessed in all recipients and defined as complete response (CR) or CR without platelet recovery (CRp). Duration of response was assessed in patients who achieved CR or CRp. Biologic activity (≥ partial response [PR]) was also recorded. Safety assessments included adverse events (AEs), concomitant medication throughout treatment, vital signs, and clinical laboratory values. Results: Eleven patients were treated in phase 1 and 32 patients in phase 2. There were 27 patients with ALL and 16 with AML. Twenty-five patients had received >3 chemotherapy regimens and 20 patients had received prior hematopoietic cell transplant in addition to chemotherapy regimens. In phase 1, 5 patients received 90 mg/m2/dose, and 6 received 120 mg/m2/dose. Because no dose-limiting toxicities were observed and therapeutic levels were obtained at 120 mg/m2, the RP2D was determined to be 120 mg/m2. In phase 2, 32 patients received 120 mg/m2. Responses in patients with ALL included 2 patients with CR at 90 mg/m2, 1 had PR, and 7 had stable disease at 120 mg/m2. Two patients with AML had stable disease at 120 mg/m2. Duration of response ranged from 1–8 months with one patient still in remission after unrelated stem cell transplant. Three deaths due to progressive disease occurred in phase 1 and 13 in phase 2. None were considered treatment-related. Thirty-seven patients had at least one grade 3 AE and 19 had at least one grade 4 AE. Twenty patients had grade 3/4 thrombocytopenia (47%), 20 had grade 3/4 anemia (46.5%), and 15 had grade 3/4 febrile neutropenia (35%). Most frequent grade 3/4 non-hematologic AEs were hyperkalemia (21%), dyspnea (9.3%), and tumor lysis syndrome (9.3%). No patients withdrew due to AEs. Conclusions: In pediatric patients with multiple relapsed and refractory ALL and AML, preliminary data suggest that bendamustine has an acceptable safety profile. The RP2D was established as 120 mg/m2, which is identical to that used to treat adults with rituximab-refractory NHL. Response data for the study population suggest that bendamustine has minimal activity in heavily pretreated patients with relapsed and refractory ALL, but not in AML. Further studies will be required to evaluate the role of this agent in combination with regimens that are the backbone of current leukemia therapy in children. This research was sponsored by and conducted by Cephalon, Inc., Frazer, PA. Disclosures: Off Label Use: Bendamustine is FDA-approved for adults with chronic lymphocytic leukemia or indolent B-cell non-Hodgkin's lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Frankel:PPD-PharmacoVigilance: Employment, PPD-PharmacoVigilance received funding from Cephalon, Inc. to perform the described analysis. Bensen-Kennedy:Cephalon, Inc.: Employment during the execution of the study. Munteanu:Cephalon, Inc.: Employment. Weaver:Cephalon, Inc.: Employment.

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Pancytopenia or Bicytopenia in a Korean Tertiary Care Center; Etiological Profile Based on Bone Marrow Examination and Suggestion for Diagnostic Approach

Blood ◽

10.1182/blood.v126.23.5610.5610 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5610-5610 ◽

Cited By ~ 1

Author(s):

Mi-Hyun Bae ◽

Young-Uk Cho ◽

Bohyun Kim ◽

Seongsoo Jang ◽

Chan-Jeoung Park ◽

...

Keyword(s):

Bone Marrow ◽

Pediatric Patients ◽

Lymphoblastic Leukemia ◽

Metastatic Cancer ◽

Care Center ◽

Tertiary Care ◽

Metastatic Carcinoma ◽

Tertiary Care Center ◽

Number Of Patients ◽

New Onset

Abstract Background: New-onset pancytopenia or bicytopenia presents a diagnostic challenge and often leads to an invasive bone marrow (BM) aspiration and biopsy. There have been several studies that determined the distribution of BM diagnoses in patients with new-onset cytopenia. However, most of these studies were performed in nations, where the nutritional and environmental status is significantly different than that of Korea. Thus, the objective of this study was to evaluate the distribution of BM diagnoses among patients at a single tertiary care center in Korea and also to provide a recommendation for a practical laboratory approach based on the distribution. Methods: We performed a search of BM data in our laboratory information system regarding new-onset pancytopenia or bicytopenia from January 2010 to December 2014. The BM diagnoses, hematological parameters, and associated clinical findings at presentation were recorded. Results: A total of 2,632 patients were referred for BM examination for bicytopenia or pancytopenia (n = 901) during the study period. Of the BM examinations for bicytopenia (n = 1,731), 1,580 were performed on adults and 151 were performed on pediatric patients. In adults, the most common BM diagnosis was a malignancy (65.8%), including acute myeloid leukemia (AML; 25.9%), BM involvement of lymphoma (12.7%), plasma cell myeloma (PCM; 8.2%), acute lymphoblastic leukemia (ALL; 6.3%), myelodysplastic syndrome (MDS; 4.4%), metastatic carcinoma (3.2%), and other malignancies (5.0%). Benign diagnoses included idiopathic thrombocytopenic purpura (ITP; 1.9%) and aplastic anemia (AA; 1.3%). Non-specific findings were present in the remaining 31.0% of patients. In children, the most common BM diagnosis was a malignancy, including ALL (45.8%), hemophagocytic lymphohistiocytosis (HLH; 18.8%), AML (12.5%), metastatic neuroblastoma (6.3%), MDS (3.3%), and others (1.0%). AA was found in 6.3%, and non-specific findings were present in 6.3% of patients. Of the BM examinations for pancytopenia (n = 901), 791 were performed on adults and 110 were performed on pediatric patients. In adults, the most common BM diagnosis was also a malignancy (50.6%), including MDS (16.5%), AML (15.2%), BM involvement of lymphoma (8.9%), ALL (6.3%), metastatic carcinoma (1.3%), and others (2.5%). Benign diagnoses included AA (10.1%) and ITP (1.3%). Non-specific findings were present in the remaining 38.0% of patients. In children, the most common BM diagnosis was also a malignancy, including ALL (36.4%), HLH (9.1%), and AML (9.1%). AA was found in 27.3%, and non-specific findings were present in 18.2% of patients. Of note, a small number of patients exhibited unique circumstances, including a lymphoma or even metastatic cancer diagnosed in the BM without an available histological diagnosis (1.8%), acute leukemia with no apparent circulating blasts (1.1%), or therapy-related myeloid neoplasms (1.1%) Conclusions: The results of this study revealed the prevalent causes of new-onset cytopenia in the Korean population and can hopefully provide diagnostic insights to both physicians and hematopathologists. Furthermore, our results could justify performing BM examination on patients with new-onset cytopenia as well as refining the diagnostic approaches such as protein electrophoresis, immunohistochemistry for lymphoma or even carcinoma, and recommendations for further imaging studies on these patients. Disclosures No relevant conflicts of interest to declare.

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Cardiotoxicity - the first cause of morbidity and mortality in pediatric patients survivors of acute lymphoblastic leukemia

Revista Romana de Medicina de Laborator ◽

10.2478/rrlm-2020-0007 ◽

2020 ◽

Vol 28 (2) ◽

pp. 133-144

Author(s):

Letitia Elena Radu ◽

Roxana Corina Sfetea ◽

Constantin Virgiliu Arion ◽

Anca Colita

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Pediatric Patients ◽

Treatment Plan ◽

Lymphoblastic Leukemia ◽

Treatment Options ◽

Myocardial Damage ◽

Morbidity And Mortality ◽

Cardiac Damage ◽

Efficient Treatment ◽

Late Cardiotoxicity

AbstractAcute lymphoblastic leukemia is the most common hematological malignancy at pediatric age. Cardiotoxicity holds the first place among the causes of morbidity and mortality in these patients. Anthracyclines are cytostatic drugs frequently associated with cardiotoxicity. Early diagnosis of cardiac impairment during the treatment of pediatric patients is extremely important, both for modulating future chemotherapy and for administering cardioprotective agents. Long term monitoring after chemotherapy helps to identify the risk of late cardiotoxicity among cancer survivors. There are several biomarkers, already in use or still under study, which may represent an operator-independent alternative for echocardiography in the diagnosis of cardiotoxicity. In case of cardiac damage, the clinician has options for treating or limiting the progression, either with the use of already approved agents, such as Dexrazoxane, or by administrating other cardioprotective drugs. International experts are still attempting to establish the best algorithm for early detection of cardiotoxicity, as well as the most efficient treatment plan in case of already existing myocardial damage in these patients. We present a review on treatment-related cardiotoxicity, including mechanisms of development, useful biomarkers and treatment options, after carefully analyzing specialty literature.

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IKZF1 Gene Deletion in Pediatric Patients Diagnosed with Acute Lymphoblastic Leukemia in Mexico

Cytogenetic and Genome Research ◽

10.1159/000499641 ◽

2019 ◽

Vol 158 (1) ◽

pp. 10-16 ◽

Cited By ~ 1

Author(s):

Miriam F. Ayón-Pérez ◽

Helia J. Pimentel-Gutiérrez ◽

Ma. de Jesús Durán-Avelar ◽

Norberto Vibanco-Pérez ◽

Víctor M. Pérez-Peraza ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Cell Cycle Progression ◽

Gene Deletion ◽

Pediatric Patients ◽

Pediatric Population ◽

Lymphoblastic Leukemia ◽

Control Cell ◽

Therapy Response ◽

Expression Of Genes ◽

Poor Treatment

The IKZF1 gene is formed by 8 exons and encodes IKAROS, a transcription factor that regulates the expression of genes that control cell cycle progression and cell survival. In general, 15-20% of the patients with preB acute lymphoblastic leukemia (preB ALL) harbor IKZF1 deletions, and the frequency of these deletions increases in BCR-ABL1 or Ph-like subgroups. These deletions have been associated with poor treatment response and the risk of relapse. The aim of this descriptive study was to determine the frequency of IKZF1 deletions and the success of an induction therapy response in Mexican pediatric patients diagnosed with preB ALL in 2 hospitals from 2017 to August 2018. Thirty-six bone marrow samples from patients at the Instituto Nacional de Pediatría in Mexico City and the Centro Estatal de Cancerología in Tepic were analyzed. The IKZF1 deletion was identified by MLPA using the SALSA MLPA P335 ALL-IKZF1 probemix. Deletions of at least 1 IKZF1 exon were observed in 7/34 samples (20.6%): 3 with 1 exon deleted; 1 with 2 exons, 1 with 5 exons, 1 with 6 exons, and 1 patient with a complete IKZF1 deletion. This study was descriptive in nature; we calculated the frequency of the IKZF1 gene deletion in a Mexican pediatric population with preB ALL as 20.6%.

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Renal involvement at diagnosis of pediatric acute lymphoblastic leukemia

Pediatric Reports ◽

10.4081/pr.2020.8382 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Mayerly Prada-Rico ◽

Carmen Inés Rodríguez-Cuellar ◽

Lucy Natalia Arteaga Aya ◽

Claudia Lorena Nuñez Chates ◽

Sandra Patricia Garces Sterling ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

Pediatric Patients ◽

Lymphoblastic Leukemia ◽

Renal Involvement ◽

Signs And Symptoms ◽

Case Review ◽

Chemotherapy Treatment ◽

Retrospective Case ◽

Extrarenal Manifestations

Acute leukemia is the most common type of cancer in pediatric patients. This type of cancer accounts for a third of all childhood cancer cases. More than half of pediatric acute leukemia patients show signs and symptoms such as hepatomegaly, splenomegaly, pallor, fever and bruising at the time of diagnosis. In early stages of acute lymphoblastic leukemia (ALL), nephromegaly and other renal manifestations such as high blood pressure (HBP) and renal failure are uncommon, although renal infiltration and nephromegaly are common in advanced-stage pediatric patients. This is a retrospective case review with a critical appraisal of the existing evidence from the literature. We present a clinical case of a child with HBP associated with bilateral nephromegaly which resolved after chemotherapy treatment. This patient presented with HBP that required pharmacological treatment, likely owing to nephromegaly. All HBP secondary causes were rejected. Nephromegaly was resolved after chemotherapy treatment, and antihypertensive medication was discontinued. Nephromegaly and HBP are rare manifestations of ALL debut in pediatrics. The present case report illustrates this unusual combination and Suggests clinicians to consider malignancy as its causal factor, especially if the symptoms are accompanied by other suggestive extrarenal manifestations.

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Multidrug resistance gene 1 polymorphisms in pediatric patients with leukemia at a national referral hospital in Indonesia

Asian Biomedicine ◽

10.5372/1905-7415.0905.432 ◽

2017 ◽

Vol 9 (5) ◽

pp. 625-630 ◽

Cited By ~ 1

Author(s):

Rina Mutiara ◽

Bernadius Agustinus ◽

Christian Badia Sitompul ◽

Amarila Malik ◽

Djajadiman Gatot ◽

...

Keyword(s):

Multidrug Resistance ◽

High Risk ◽

Resistance Gene ◽

Pediatric Patients ◽

Risk Group ◽

Pediatric Population ◽

Lymphoblastic Leukemia ◽

High Risk Group ◽

Multidrug Resistance Gene ◽

Standard Risk

Abstract Background Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in the pediatric population. From 25% to 30% of patients with ALL will have a relapse that leads to death when they are teenagers. At Cipto Mangunkusumo Hospital, 40% of 126 pediatric patients with ALL relapsed from 2005 to 2011. A multiple variant of multidrug resistance gene 1 (MDR1) is C3435T, which can be used to understand the genetic basis of susceptibility to relapse. Objectives To identify the profile of MDR1 polymorphism in pediatric Indonesian patients with ALL. Methods We collected data from 44 patients with ALL who attended Cipto Mangunkusumo Hospital between January and June 2014. We investigated a silent C3435T polymorphism in MDR1 exon 26 with polymerase chain reaction- restriction fragment length polymorphism using MboI. Results There were 32 male and 12 female patient participants in this study. Eighteen patients were 1–3 years old and 26 were over 3 years. The mean age at 1–3 years was 2.4 ± 0.86, and over 3 years it was 6.3 ± 2.67 years. There were 27 patients with ALL in the standard risk group and 17 in the high risk group. We determined that the 25 samples from patients with ALL in the standard risk group were not digestible (allele T) and the 6 samples from patients with ALL in the high risk group were digestible (allele C). Conclusions The prevalence of the T allele was higher than that of the C allele in pediatric Indonesian patients with ALL.

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Clofarabine in Pediatric Patients with Refractory or Relapsed Leukemia: the GATLA experience.

Blood ◽

10.1182/blood.v120.21.2605.2605 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2605-2605

Author(s):

David Veron ◽

Cecilia Riccheri ◽

Monica Makiya ◽

Luis Alberto Aversa ◽

Marcela Gutierrez ◽

...

Keyword(s):

Acute Leukemia ◽

Progressive Disease ◽

Pediatric Patients ◽

Lymphoblastic Leukemia ◽

The Other ◽

Refractory Disease ◽

Hematopoietic Stem ◽

First Relapse ◽

Disease Free

Abstract Abstract 2605 Introduction: The outcome in pediatric patients with relapse-refractory acute leukemia (acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)) is very poor. Clofarabine is an active agent in this high risk group. Purpose: Report the GATLA experience in patients with relapse-refractory acute leukemia treated with clofarabine based regimens. Methods: Between June 07 and April 12, 66 patients from 15 GATLA centers were enrolled. 61 ALL (52 B/9 T): 23 first relapse (20 BM, 1 CNS, 2 combined), 33 second relapse (28 BM, 1 CNS, 4 combined), 5 with refractory disease. 5 AML (4 first relapse, 1 refractory disease). Median age 10,5 years (1–20 ys). Gender: 44 boys and 22 girls. 60 patients received chemotherapy combined clofarabine-etoposide-cyclophosphamide (CLO 218), 4 patients received clofarabine plus ara-c therapy and 2 patients were treated with clofarabine alone (52mg/m2). 63.7% (42/66) of the patients were treated with 2 therapeutic lines prior to clofarabine regimens, 22.7% (15/66) received only 1 prior treatment, 13.6% (9/66) got 3 or more therapies and 5 patients undergone prior HSCT (Hematopoietic Stem Cell Transplantation). Results: Complete remission (CR) was achieved in: 36/66 patients (54,5 %). Early toxic death rate was 7/66 (10,6%). No response occurred in 22/66 (33,3%) patients. 1 patient is on induction, not evaluable at the moment. Of the 36 responders, 19 patients (52,7 %) proceeded to HSCT: 6 (31,5 %) remain alive post-transplantation with a median follow up of 55 weeks ( range 6–156 w), HSCT related death: 7 (37 %), relapse after HSCT: 6 (31,5%) at a mean of 20 weeks( range 8–56 weeks). Among the 61 ALL patients, 18/23 (78%) in first relapse achieved CR, 12/18 (66,6%) needed only one course to achieved CR, of them, 3/12 (25%) relapsed at 8, 8 and 14 weeks and died for progressive disease. 1/12 (8,3%) died in CR at week 8. 2/12 (16,6%) patients are on treatment. 6/12 (50%) proceeded to HSCT: 1/6 relapsed 56 weeks after. 3/6 patients died in CR after HSCT at 12, 15 and 24 weeks. 2/6 remain in CR at 6 weeks follow up. 6/18 (33,3%) of the patients in first relapse needed 2 courses to achieved CR. 1/6 (16,7%) relapsed at week 8. 2/6(33,3%) died in CR at week 9 and 16. 3/6 ( 50%) proceeded to HSCT, 1 is alive at 36 weeks, 1 relapsed at week 26 and 1 died in CR at week 14. 13/33 (39%) ALL patients in second relapse achieved CR and 8/13 (61,5%) needed only one course to CR. 3/8 (37,5%) relapsed at 6,8 and 16 weeks and died for progressive disease. 5/8(62,5%) proceeded to HSCT, of them 3 (60%) relapsed after HSCT at 8,8 and 12 weeks. 1/5 (20%) is alive and disease free at 6 weeks after HSCT. 1/5 (20%) died in CR. 5/13 (38%) needed 2 courses to achieved CR, 1/5 relapsed after 4 weeks. 1/5 died in CR at week 6, 1/5 is alive 40 weeks after CR. 2/5 proceeded to HSCT and died in CR at 10 and 22 weeks after HSCT. 2/5 ALL patients with refractory disease achieved CR with 2 and 3 courses of clofarabine, one proceeded to HSCT and is alive with a follow up of 156 weeks, the other relapsed at 8 weeks. 3/5 did not response and died. AML patients: 3/5 received clofarabine as 3rd therapeutic line: 1 patient achieved CR after one course but died of toxicity, 1 patient did not response and 1 died during induction. 2/5 received clofarabine as 2ndline ( 1 with refractory disease and 1 who undergone prior HSCT), they achieved CR with 2 courses of chemotherapy and proceeded to HSCT, one relapsed after 16 weeks and the other is alive and disease free after 120 weeks. Conclusion: In our series, Clofarabine was well tolerated and shows significant antileukemic activity in heavily pretreated children. The response rate and the durability of remission observed is better when clofarabine regimens are used earlier (first relapse). Responses allowed several refractory patients to proceed to HSCT. Levels of pre transplant MRD (Minimal Residual Disease)should be taken into account in order to follow this procedure. Disclosures: No relevant conflicts of interest to declare.

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