scholarly journals Blood Product Requirement in Childhood Acute Lymphoblastic Leukemia in Relation to Chemotherapy Regimens

2020 ◽  
Vol 30 (3) ◽  
Author(s):  
Elif Gudeloglu ◽  
Davut Albayrak
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Blood Product ◽  
Lymphoblastic Leukemia ◽  
Study Data ◽  
Blood Product Transfusion ◽  
Erythrocyte Transfusion ◽  
Platelet Suspension ◽  
Product Use ◽  
Transfusion Requirements ◽  
Significant Difference

Background: Along with lack of studies that systematically address the transfusion requirements and triggers in acute leukemia, no study to date has addressed the blood product use with respect to ongoing chemotherapy (CT) in pediatric acute lymphoblastic leukemia (ALL) patients. Objectives: This study was therefore designed to evaluate total erythrocyte, random platelet and apheresis platelet suspension requirement in pediatric ALL patients in relation to ongoing CT protocols. Methods: A total of 146 pediatric patients with ALL were included in this retrospective study. Data on patient demographics, CT protocol, amount and efficacy of blood product use (erythrocytes, apheresis platelet and random platelet), and survival during CT were retrieved from hospital records. Results: The average amount of erythrocytes, apheresis platelets and random platelets received by 146 ALL patients from the date of diagnosis were 14 (3 - 78) bags, 9 (1 - 97 bags and 11 (1 - 83) bags, respectively. Protocol 1b augmented was associated with the highest amount of erythrocyte use (P < 0.001), while no significant difference was noted in apheresis platelet and random platelet use with respect to CT regimens. Erythrocyte transfusion was associated with a more marked increase in hemoglobin (Hb), erythrocyte (RBC), leukocyte (WBC), lymphocyte and neutrophil counts as compared with apheresis platelet and random platelet infusions, while protocol 2 was associated with higher Hb (P = 0.017) levels after erythrocyte transfusion. Conclusions: Our findings indicate a great amount of blood product transfusion to be required in children with ALL under CT and emphasize the likelihood of transfusion need and efficacy of transfusion to alter with respect to ongoing CT regimen. The need in patients using augmented BFM protocol 1 b was highest, and albeit the need of blood and blood product transfusions vary within patients, the anticipated median need for blood products at diagnosis and at various blocks of treatment may be helpful for the blood banks, doctors of the respective pediatric hematology-oncology centers to plan as patients are treated.

scholarly journals Increased Levels of Adipocyte and Epidermal Fatty Acid-Binding Proteins in Acute Lymphoblastic Leukemia Survivors

2021 ◽  
Vol 10 (8) ◽  
pp. 1567
Author(s):  
Katarzyna Konończuk ◽  
Eryk Latoch ◽  
Beata Żelazowska-Rutkowska ◽  
Maryna Krawczuk-Rybak ◽  
Katarzyna Muszyńska-Rosłan
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Acute Lymphoblastic Leukemia ◽  
Binding Proteins ◽  
Lymphoblastic Leukemia ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Significant Difference

Childhood cancer survivors are highly exposed to the development of side effects after many years of cessation of anticancer treatment, including altered lipid metabolism that may result in an increased risk of overweight and metabolic syndrome. Adipocyte (A-FABP) and epidermal (E-FABP) fatty acid-binding proteins are expressed in adipocytes and are assumed to play an important role in the development of lipid disturbances leading to the onset of metabolic syndrome. The aim of this study was to investigate the association between serum A-FABP and E-FABP levels, overweight, and components of the metabolic syndrome in acute lymphoblastic leukemia survivors. Sixty-two acute lymphoblastic leukemia (ALL) survivors (34 females) were included in the study. The mean age at the time of the study was 12.41 ± 4.98 years (range 4.71–23.43). Serum levels of A-FABP and E-FABP were analyzed using a commercially available ELISA kit. The ALL survivors presented statistically higher A-FABP levels in comparison with the healthy controls (25.57 ± 14.46 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with body mass index (BMI) above the normal range (18 overweight, 10 obese) had a greater level of A-FABP compared to the ALL group with normal BMI (32.02 ± 17.10 vs. 20.33 ± 9.24 ng/mL, p = 0.006). Of all participants, 53.23% had at least one risk factor of metabolic syndrome; in this group, only the A-FABP level showed a statistically significant difference compared to the healthy control group (30.63 ± 15.91 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with two or more metabolic risk factors (16.13%) presented higher levels of both A-FABP (33.62 ± 17.16 vs. 15.13 ± 7.61 ng/mL, p = 0.001) and E-FABP (13.37 ± 3.62 vs. 10.12 ± 3.21 ng/mL, p = 0.021) compared to the controls. Univariable regression models showed significant associations between BMI and systolic blood pressure with the A-FABP level (coeff. 1.02 and 13.74, respectively; p < 0.05). In contrast, the E-FABP level was only affected by BMI (coeff. 0.48; p < 0.01). The findings reported herein suggest that the increased levels of A-FABP and E-FABP may be involved in the pathogenesis of overweight and the onset of metabolic syndrome in acute lymphoblastic leukemia. However, further longitudinal, prospective studies of fatty acid-binding proteins and their potential role in the pathogenesis of obesity and metabolic syndrome in ALL survivors remain to be performed.

Desmopressin Reduces Transfusion Needs after Surgery

2008 ◽  
Vol 109 (6) ◽  
pp. 1063-1076 ◽  
Author(s):  
Giuseppe Crescenzi ◽  
Giovanni Landoni ◽  
Giuseppe Biondi-Zoccai ◽  
Federico Pappalardo ◽  
Massimiliano Nuzzi ◽  
...  
Keyword(s):  
Blood Loss ◽  
Excess Mortality ◽  
Blood Product ◽  
Meta Analysis ◽  
Blood Product Transfusion ◽  
Blood Products ◽  
Hemostatic Agents ◽  
Randomized Controlled ◽  
Randomized Controlled Studies ◽  
Transfusion Requirements

Background Perioperative pathologic microvascular bleeding is associated with increased morbidity and mortality and could be reduced by hemostatic drugs. At the same time, safety concerns regarding existing hemostatic agents include excess mortality. Numerous trials investigating desmopressin have lacked power to detect a beneficial effect on transfusion of blood products. The authors performed a meta-analysis of 38 randomized, placebo-controlled trials (2,488 patients) investigating desmopressin in surgery and indicating at least perioperative blood loss or transfusion of blood products. Methods Pertinent studies were searched in BioMed Central, CENTRAL, and PubMed (updated May 1, 2008). Further hand or computerized searches involved recent (2003-2008) conference proceedings. Results In most of the included studies, 0.3 microg/kg desmopressin was used prophylactically over a 15- to 30-min period. In comparison with placebo, desmopressin was associated with reduced requirements of blood product transfusion (standardized mean difference = -0.29 [-0.52 to -0.06] units per patient; P = 0.01), which were more pronounced in the subgroup of noncardiac surgery and were without a statistically significant increase in thromboembolic adverse events (57/1,002 = 5.7% in the desmopressin group vs. 45/979 = 4.6% in the placebo group; P = 0.3). Conclusions Desmopressin slightly reduced blood loss (almost 80 ml per patient) and transfusion requirements (almost 0.3 units per patient) in surgical patients, without reduction in the proportion of patients who received transfusions. This meta-analysis suggests the importance of further large, randomized controlled studies using desmopressin in patients with or at risk of perioperative pathologic microvascular bleeding.

scholarly journals Effects of TPMT, NUDT15, and ITPA Genetic Variants on 6-Mercaptopurine Toxicity for Pediatric Patients With Acute Lymphoblastic Leukemia in Yunnan of China

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaoyan Mao ◽  
Runxiu Yin ◽  
Gaoyuan Sun ◽  
Yan Zhou ◽  
Chunhui Yang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Yunnan Province ◽  
Medical Center ◽  
Lymphoblastic Leukemia ◽  
Free Survival ◽  
Ethnic Populations ◽  
Significant Difference ◽  
Pediatric All ◽  
Medical University ◽  
Tolerable Dose

Background: 6-Mercaptopurine (6-MP) is the cornerstone of current antileukemia regimen and contributes greatly to improve the survival of pediatric acute lymphoblastic leukemia (ALL) patients. However, 6-MP dose-related toxicities limit its application. TPMT, NUDT15, and ITPA are pharmacogenetic markers predicting 6-MP-related toxicities, but their genetic polymorphisms differ from those of ethnic populations. In Yunnan province, a multiethnic region of China, we had no genetic data to predict 6-MP toxicities. In this study, we evaluated the most common variants involved in 6-MP metabolism—TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) variants—in our cohort of pediatric ALL patients.Methods: A total of 149 pediatric ALL patients in the Affiliated Children's Hospital of Kunming Medical University (Yunnan Children's Medical Center) from 2017 to 2019 were enrolled in this retrospective study. We assessed the TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) frequencies and evaluated association between genotypes and 6-MP toxicities, 6-MP dose, and event-free survival (EFS) in these ALL patients.Results: The allele frequencies of TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) were 1.34%, 14.43%, and 18.79%, respectively. Only NUDT15 c.415C&gt;T (rs116855232) was strongly associated with 6-MP toxicity and 6-MP tolerable dose. NUDT15 c.415C&gt;T was related to leukopenia, p = 0.008, OR = 2.743 (95% CI: 1.305–5.768). The T allele was significantly correlated with 6-MP tolerable dose, dose of NUDT15 c.415C&gt;T wild genotype CC 39.80 ± 1.32 mg/m2, heterozygotes CT 35.20 ± 2.29 mg/m2, and homozygotes TT 18.95 ± 3.95 mg/m2. 6-MP tolerable dose between CC and TT had a significant difference, p = 0.009. Between CC and CT, and CT and TT, they had no significant difference. EFS showed no significant difference among NUDT15 c.415C&gt;T genotypes.Conclusion:NUDT15 c.415C&gt;T (rs116855232) was an optimal predictor for 6-MP toxicity and tolerable dose in pediatric ALL patients from Yunnan province, a multiethnic region in China, and would play an important role in precise therapy for ALL.

Intensification With Intermediate-Dose Intravenous Methotrexate Is Effective Therapy for Children With Lower-Risk B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study

2000 ◽  
Vol 18 (6) ◽  
pp. 1285-1294 ◽  
Author(s):  
Donald H. Mahoney ◽  
Jonathan J. Shuster ◽  
Ruprecht Nitschke ◽  
Stephen Lauer ◽  
C. Philip Steuber ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Effective Therapy ◽  
Remission Induction ◽  
Intrathecal Therapy ◽  
Continuation Therapy ◽  
Increased Risk ◽  
Significant Difference ◽  
Prevention Of Relapse

PURPOSE: To determine whether early intensification with 12 courses of intravenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 12 courses of IV MTX alone for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction therapy. Patients were randomized to receive intensification with IV MTX 1,000 mg/m2 plus IV MP 1,000 mg/m2 (regimen A) or IV MTX 1,000 mg/m2 alone (regimen C). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and triple intrathecal therapy every 12 weeks for 2 years. RESULTS: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The estimated 4-year overall continuous complete remission for patients treated with regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P = .5). No significant difference in overall outcome was shown by sex or race. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen. CONCLUSION: Intensification with 12 courses of IV MTX is an effective therapy for prevention of relapse in children with B-precursor ALL who are at lower risk for relapse but may be associated with an increased risk for neurotoxicity. Prolonged infusions of MP combined with IV MTX did not provide apparent advantage.

scholarly journals Comparison of chemotherapy with immunotherapy for maintenance of acute lymphoblastic leukemia in children and adults

Blood ◽  
1983 ◽  
Vol 62 (3) ◽  
pp. 606-615 ◽  
Author(s):  
PA Stryckmans ◽  
J Otten ◽  
MJ Delbeke ◽  
S Suciu ◽  
D Fiere ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Consolidation Chemotherapy ◽  
Disease Free Interval ◽  
Free Interval ◽  
Significant Difference ◽  
The Difference ◽  
To Receive ◽  
Disease Free ◽  
Leukemia In Children

Abstract Two hundred and seventeen patients, 1–50 yr old, with acute lymphoblastic leukemia in complete remission were randomized to receive a 1-yr consolidation chemotherapy of either type P, comprising 7 different drugs, or type M, consisting of methotrexate interspersed with prednisone and vincristine. Thereafter, they were randomized a second time to receive a 4-yr maintenance of either chemotherapy or immunotherapy, comprised of allogeneic blasts and bacillus Calmette- Guerin (BCG). Consolidation P caused more toxicity than consolidation M. However, comparison between the consolidation therapies P and M showed no significant difference, neither for disease-free interval nor for duration of survival. Chemotherapy showed more lethal toxicity in adults than in children. Comparison between chemotherapy (C) and immunotherapy (I) as maintenance treatment showed a significant (p = 0.016) superiority of C for disease-free interval (DFI). The difference was even more pronounced (p = 0.009) in the group with less than 8 g/dl of hemoglobin (Hb) at diagnosis before therapy. On the other hand, for patients with more than 8 g/dl Hb at diagnosis, presumably those with T- ALL, no difference in DFI was seen. No difference has been seen so far between maintenance therapies I and C concerning the duration of survival. The patients who were receiving maintenance I when they relapsed and who were consequently retreated by chemotherapy, survived longer from relapse than those patients retreated for relapse while receiving maintenance C.

Prehospital Blood Product Administration Opportunities in Ground Transport ALS EMS – A Descriptive Study

2018 ◽  
Vol 33 (3) ◽  
pp. 230-236 ◽  
Author(s):  
Felicia M. Mix ◽  
Martin D. Zielinski ◽  
Lucas A. Myers ◽  
Kathy S. Berns ◽  
Anurahda Luke ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Patient Care ◽  
Blood Product ◽  
Life Support ◽  
Descriptive Study ◽  
Blood Product Transfusion ◽  
Trauma Patients ◽  
Blood Products ◽  
Total Patient ◽  
Significant Difference

AbstractIntroductionHemorrhage remains the major cause of preventable death after trauma. Recent data suggest that earlier blood product administration may improve outcomes. The purpose of this study was to determine whether opportunities exist for blood product transfusion by ground Emergency Medical Services (EMS).MethodsThis was a single EMS agency retrospective study of ground and helicopter responses from January 1, 2011 through December 31, 2015 for adult trauma patients transported from the scene of injury who met predetermined hemodynamic (HD) parameters for potential transfusion (heart rate [HR]≥120 and/or systolic blood pressure [SBP]≤90).ResultsA total of 7,900 scene trauma ground transports occurred during the study period. Of 420 patients meeting HD criteria for transfusion, 53 (12.6%) had a significant mechanism of injury (MOI). Outcome data were available for 51 patients; 17 received blood products during their emergency department (ED) resuscitation. The percentage of patients receiving blood products based upon HD criteria ranged from 1.0% (HR) to 5.9% (SBP) to 38.1% (HR+SBP). In all, 74 Helicopter EMS (HEMS) transports met HD criteria for blood transfusion, of which, 28 patients received prehospital blood transfusion. Statistically significant total patient care time differences were noted for both the HR and the SBP cohorts, with HEMS having longer time intervals; no statistically significant difference in mean total patient care time was noted in the HR+SBP cohort.ConclusionsIn this study population, HD parameters alone did not predict need for ED blood product administration. Despite longer transport times, only one-third of HEMS patients meeting HD criteria for blood administration received prehospital transfusion. While one-third of ground Advanced Life Support (ALS) transport patients manifesting HD compromise received blood products in the ED, this represented 0.2% of total trauma transports over the study period. Given complex logistical issues involved in prehospital blood product administration, opportunities for ground administration appear limited within the described system.MixFM, ZielinskiMD, MyersLA, BernsKS, LukeA, StubbsJR, ZietlowSP, JenkinsDH, SztajnkrycerMD. Prehospital blood product administration opportunities in ground transport ALS EMS – a descriptive study. Prehosp Disaster Med. 2018;33(3):230–236.

Study on the Phenotype Polymorphism of CYP3A4 Gene in Chinese Children with Acute Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4376-4376
Author(s):  
Xiao-jun Yuan ◽  
Long-Jun Gu ◽  
Hui-jun Zhao ◽  
Jin-cai Zhao ◽  
Jing-Yan Tang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Healthy Children ◽  
Cyp3a4 Activity ◽  
Significant Difference ◽  
Average Activity ◽  
Cyp3a4 Gene ◽  
Wbc Count

Abstract In order to offer objective refering paramete for individualized chemotherapy, to clarify the distribution feature of CYP3A4 activity in Chinese children with acute leukemia and in healthy children, to explore the possible correlation between the activity of CYP3A4 gene and the predisposition or chemotherapy effect in acute leukemia children. High performance liquid chromatography (HPLC) was used to detecte the activity of CYP3A4 in 85 healthy children and 120 acute leukemia children, then analyzed the difference of phenotypebetween two groups. The activity coverage of CYP3A4 was 2.34~48.88 in healthy children and the average activity was 9.76±6.99. Among them, CYP3A4 activity was 11.88±8.88 in male group and 7.12±3.37 in female group, the former was obviously higher than the latter (P=0.0077). In less than 12-years group, CYP3A4 activity was 8.97±6.27, while it was 10.43±7.74 in more than 12-years group, there was no significant difference (P&gt;0.05). The change scope of CYP3A4 activity was very large in children with acute lymphoblastic leukemia, from 2.00 to 585.72, the average activity was 53.52, with no dfference in sex and age. According to the clinical risk degree, the activity of CYP3A4 was 4.87±2.93 in standard-risk group, it was 31.63±19.20 in middle-risk group, the latter was significantly higher thanthe former (P=0.0004). Comparison based on WBC count at the beginning of preliminary diagnosis, the CYP3A4 activity was the lowest in WBC count less than 50 x 109/L group, it was second in the group of WBC count between 50 x 109/L to 100 x 109/L, and the activity was the highest in WBC count more than 100 x 109/L group. The mean activity of CYP3A4 in childern with acute lymphoblastic leukemia with P170 less than 5% was 17.56±13.44, while it was 87.62±49.28 in those children with P170 more than 5%Ä, there was statistic difference between the two group(P=0.022). The activity in those preliminary diagnosed children with BCR-ABL(+) or Ph (+) or t (4,11) abnormal karyotype (105.86±44.41) was higher than those with normal karyotype patients (47.61±22.63), P=0.0219. Comparison the activity of CYP3A4 between those chlidren with clinical presentation as prednisone good response (PGR) and those with prednisone poor response, the activity in former group (27.23±13.58) was obviously lower than that of latter group (114.12±48.39), P=0.0358. The average CYP3A4 activity in children with acute myelocytic leukemia (AML) was 13.97±10.84. Of them, it was 15.09±7.52 in AML children with diploid chromosome and only 2.95±1.39 in hypodiploidy group, obviously, the activity of former group higher than that of latter group (P=0.0132). The CYP3A4 activity was respectively 19.78±11.59 and 2.86±1.16 in normal LDH group and in increased LDH group, there was significant difference (P=0.0036). The AML children with exo-marrow infiltration when diagnosis, their CYP3A4 activity (6.50±3.05) was lower than those children with pure marrow infiltration (19.06±11.15), P=0.044. There may be no race difference between the CYP3A4 activity of Chinese healthy children and White people. Increased CYP3A4 activity has closed correlation with ALL risk factors. The general CYP3A4 activity in AML children group was lower than that of ALL chlidren group. Much higher or much lower CYP3A4 activity may produce adverse influence to individuals.

Varicella Vaccine (VarilRix) in Children with Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4436-4436
Author(s):  
Teresa Jackowska Ass ◽  
Robert Wasilewski ◽  
Elzbieta Górska ◽  
Maria Wasik ◽  
Teresa Loch
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Lymphocytes ◽  
Lymphoblastic Leukemia ◽  
Varicella Vaccine ◽  
White Blood Cells ◽  
Healthy Children ◽  
Varicella Zoster ◽  
Significant Difference ◽  
Before And After ◽  
History Of

Abstract Background: To assess the effectiveness of vaccination against varicella in children with acute lymphoblastic leukemia (ALL). Methods: 105 children without a history of varicella, were qualified for immunization against varicella with VARILRIX (Oka-strain varicella vaccine). 48 children had ALL and 57 were healthy. 25 of the children with ALL were receiving maintenance therapy, 23 children were after chemotherapy. Results: White blood cells (WBC), lymphocytes, and sub-populations of T- and B-lymphocytes were compared in the healthy and leukemic children before and after vaccination. The ALL children had significantly lower counts of WBC and lymphocytes before vaccination. After vaccination there were no significant differences in the counts of WBC in the healthy and leukemic children. However the ALL children had significantly lower mean counts of lymphocytes. Before vaccination the leukemic children showed a significantly lowered percentage of T-lymphocytes with decreased CD4+ and increased CD8+, what resulted in a lowered CD4 to CD8 ratio. After vaccination, only increased numbers of T CD8+ lymphocytes and a lowered CD4 to CD8 ratio were present while there was no significant difference in CD4. In the healthy and leukemic children alike there was no statistically significant difference between B-lymphocytes (CD 19+) and NK cells. In 10 children (20%), out of the 48 ALL vaccines, varicelliform rash occurred ~1 month after immunization. No adverse effects we observed in healthy children. Seroconversion to varicella-zoster virus was higher in healthy children and ALL children who had skin rash after vaccination. Two ALL children and three healthy ones had varicella one-two years after the vaccination. Those children received only single vaccine doses (double vaccine doses received children above 12 years). Conclusion: Varicella vaccine was safe and immunogenic in leukemic children during maintenance and after chemotherapy.

Intrathecal Liposomal Cytarabine (Depocyt) Is Safe and Effective for Prevention of Meningeal Disease in Patients with Acute Lymphoblastic Leukemia and High-Grade Lymphoma Treated with the HyperCVAD Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4594-4594 ◽  
Author(s):  
Brian McClune ◽  
Francis Buadi ◽  
Naveed Aslam ◽  
Donna Przepiorka
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adverse Events ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Liposomal Cytarabine ◽  
High Grade ◽  
Platelet Recovery ◽  
Significant Difference ◽  
Meningeal Disease

Patients with acute lymphoblastic leukemia (ALL) and high-grade lymphoma have a 10–20% risk of meningeal disease during induction and in remission when given standard-dose chemotherapy. This risk has been reduced to about 1% using intrathecal prophylaxis with cytarabine and methotrexate in addition to the systemic regimen of hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyperCVAD) alternating with high-dose methotrexate-cytarabine (MA). The discomfort and potential adverse events with frequent lumbar punctures may impair patient compliance. Liposomal cytarabine (Depocyt) is an intrathecal preparation of cytarabine with a prolonged half-life. Use of Depocyt could potentially reduce the number of lumbar punctures needed for routine neuroprophylaxis. We reviewed the tolerability and activity of Depocyt for neuroprophylaxis in 15 patients treated with the hyperCVAD regimen. The cohort included 12 males and 3 females of median age 48 years (range, 23–72 years) with precursor B-cell ALL (8), T-cell ALL (3), Burkitt lymphoma and HIV (2), Ph-positive ALL (1), and lymphoblastic lymphoma (1). The patients received a total of 65 cycles of systemic chemotherapy, 36 with hyperCVAD and 29 with MA. Depocyt was given IT or IO in 33 cycles, methotrexate IT in 5, and no intrathecal therapy in 27. When treated with Depocyt, patients also received dexamethasone pre- and postmedication.. The planned dose of Depocyt was 50 mg for all patients, but after one serious adverse event, the dose was reduced to 25 mg when administered by Omaya. Depocyt was instilled on a median of day 8 of the cycle (range, −4 to 13). To date, a meningeal relapse has not occurred in any of the patients. Although minor neurological events (transient headache or neckache) were not uncommon, there were two serious adverse events. One patient developed a severe but transient headache during the fourth cycle and was readmitted for pain control. A second patient received Depocyt four days prior to MA. Shortly after completing chemotherapy, this patient developed hyponatremia and somnolence. The neurological status normalized after several days with supportive care alone. Since leakage of Depocyt into the peripheral blood might cause myelosuppression, hematologic recovery was also assessed. There was a significant difference in time to ANC>500 (p=0.02) and platelets >20,000 (p=0.005) between hyperCVAD and MA cycles, so hematologic recovery was assessed separately for these regimens, as shown in the Table. Median Day of Hematopoietic Recovery Cycle Outcome All Cycles Depocyt No IT PX MTX IT “1” indicates the platelet count did not fall below 20,000 during that cycle. HyperCVAD ANC>500 15 15 14 16.5 Plts>20,000 1 1 1 1 MA ANC>500 16 16 16 15 Plts>20,000 13 13 14 15 There were no significant differences in time to neutrophil or platelet recovery between neuroprophylaxis regimens. Three patients received cranial or craniospinal radiation to compete neuroprophylaxis prior to allogeneic stem cell transplantation without notable neurotoxicity after transplantation. We conclude that it is safe to use a single dose of Depocyt (50 mg IT or 25 mg IO) following completion of administration of chemotherapy (around Days 6 – 8) during each cycle of the hyperCVAD regimen. This approach should be studied in a randomized trial to further assess its efficacy in comparison to more frequent instillations of methotrexate/cytarabine.

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