scholarly journals Effect of glucocorticoid therapy on adrenal function in children with acute lymphoblastic leukemia

2014 ◽  
Vol 54 (1) ◽  
pp. 15
Author(s):  
Gita Widyapuri ◽  
Djajadiman Gatot ◽  
Aman Bakti Pulungan ◽  
Badriul Hegar
Keyword(s):  
Hpa Axis ◽  
Standard Dose ◽  
Lymphoblastic Leukemia ◽  
Adrenal Function ◽  
High Dose ◽  
Induction Phase ◽  
Acth Test ◽  
Before And After ◽  
Response To Stress ◽  
Cortisol Levels

BackgroundGlucocorticoids play an important role in thetreatment ofacute lymphoblastic leukemia (ALL), but can causeside effects such as suppression of the hypothalamic-pituitaryadrenal (HPA) axis. Suppression of the HPA axis causes adrenal insufficiency, disturbs the cortisol response to stress, and may be a cause of morbidity and mortality in children with ALL.ObjectiveTo evaluate adrenal function in children with ALL afterinduction chemotherapy with high dose glucocorticoids.MethodsThe adrenal function of 20 children with ALL wasevaluated using a standard dose (250 μ g) adrenocorticotropinhormone (ACTH) test performed before and after a 6 week oftreatment with glucocorticoids induction phase chemotherapy,which was followed by a week period tapering off. Adrenalinsuffien cy was defined as blood cortisol level of < 18 μg/dLResultsAdrenal insufficiency was found in 14/20 subjects afterthe induction phase followed by a week period of tapering off.Median cortisol levels pre- and post-stimulation before inductionphase were 14.72 (range 2.0 1- 46. 1) μg/dL and 29.29 (range 21.65 - 55 .15) μg/dL, respectively. Median cortisol levels pre- and poststimulation after induction phase were 5.87 (range 0.2 - 20.53)μg/dL and 10.49 (range 0.33 - 28.69) μg/dL, respectively. Clinicalsigns and symptoms did not differ between those with and withoutadrenal insufficiency.ConclusionOf 20 children with ALL, 14 develop adrenalinsufficiency after a 6-week induction therapy with glucocorticoidsand followed by a week period of tapering off. No specific clinicalsigns and symptoms are identified to be related to the adrenalinsufficiency.

scholarly journals Peripheral cortisol administration blunts reward arousal but heightens anxiety-like arousal in marmosets

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S163-S164
Author(s):  
Laith Alexander ◽  
Philip Gaskin ◽  
Lauren McIver ◽  
Angela Roberts
Keyword(s):  
Unconditioned Stimulus ◽  
Hpa Axis ◽  
Saline Control ◽  
Subcutaneous Injections ◽  
Video Cameras ◽  
Before And After ◽  
Control Versus ◽  
Cortisol Levels ◽  
Future Work ◽  
Cardiovascular Arousal

AimsExcess hypothalamic-pituitary-adrenal (HPA) axis activation is common in people with major depression and generalised anxiety disorder. We sought to determine whether higher circulating levels of the glucocorticoid cortisol are causally related to the expression of anhedonia-like and anxiety-like behaviours in marmosets.MethodFour marmosets (two male, two female) took part in the study. Cortisol and saline control injections were administered intramuscularly and salivary cortisol samples were taken before and after injections to determine if circulating cortisol levels changed from pre- to post-injection. To measure anhedonia-like behaviours, we trained marmosets on an appetitive Pavlovian conditioning paradigm, where animals learn to associate two anticipatory auditory cues (conditioned stimulus + or conditioned sitmulus -, CS+ or CS-) with the presence or absence of food reward (unconditioned stimulus + or unconditioned stimulus -, US+ or US-). Using cardiovascular telemetry probes and video cameras, we recorded animals' cardiovascular and behavioural arousal in freely moving conditions, comparing the injection of saline control versus 5mg/kg, 10mg/kg or 20mg/kg intramuscular cortisol. To measure anxiety-like behaviours, we used a human intruder (HI) paradigm, where marmosets are confronted with an unfamiliar human in their home cage. We recorded their behaviour on video cameras after saline control or 20mg/kg intramuscular cortisol. We used an exploratory-factor analysis (EFA) to determine how marmosets' behaviours towards the intruder loaded onto an 'anxiety-like' score. We then compared these scores under saline control versus cortisol conditions. Significance was set at p < 0.05.ResultUnlike saline control, we found that subcutaneous injections of 20 mg/kg cortisol successfully elevated peripheral cortisol concentrations to levels equivalent to peak circadian concentrations (p = 0.023). In the appetitive setting, 5 mg/kg, 10 mg/kg and 20 mg/kg cortisol injections blunted anticipatory (CS+ induced) increases in behavioural arousal (p = 0.004) but did not alter anticipatory cardiovascular arousal. Consummatory behavioural and cardiovascular arousal also remained intact. In the HI test, 20 mg/kg cortisol injections moderately increased anxiety towards the intruder as measured by an increase in marmosets' EFA-derived anxiety-like scores (p = 0.035).ConclusionIn marmosets, elevated peripheral cortisol levels are causally related to the behavioural features of blunted reward anticipation together with elevated anxiety-like behaviours characteristic of mood and anxiety disorders. Future work will characterise the neuroimaging changes induced by elevated peripheral cortisol levels and identify the regions of the prefrontal cortex contributing to HPA axis regulation and dysregulation.

Chemoimmunotherapy with a Modified Hyper-CVAD and Rituximab Regimen Improves Outcome for Patients with De Novo Philadelphia Negative Precursor B-Cell Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 836-836
Author(s):  
Deborah A. Thomas ◽  
Hagop M. Kantarjian ◽  
Stefan Faderl ◽  
William G. Wierda ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
High Dose ◽  
Induction Phase ◽  
Liposomal Daunorubicin ◽  
Cd20 Expression

Abstract Abstract 836 The hyper-CVAD regimen is an effective frontline program for de novo adult ALL and LL [Kantarjian, JCO 18:547, 2000; Kantarjian, Cancer 101:2788, 2004, Thomas, Blood 104:1624, 2004]. Intensive chemotherapy with hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin, dexamethasone) alternates with high dose methotrexate (MTX) and cytarabine every 21 days for 8 courses, followed by maintenance therapy with POMP (6-mercaptopurine, MTX, VCR, prednisone). Historical CR rate was 92% with 3-year disease-free survival (DFS) rate of 38%. The regimen was modified in 1999. Induction chemotherapy was given in a protective environment owing to higher mortality in patients (pts) aged 60 years or older (17% vs 3%). Course 2 of liposomal daunorubicin and cytarabine was incorporated owing to reports suggesting benefit of early anthracycline intensification. Rituximab 375 mg/m2 (days 1 & 11 of hyper-CVAD, days 1 & 8 of methotrexate-cytarabine) was given if CD20 expression was 20% or greater due to its association with disease recurrence [Thomas, Blood 113:6330, 2009]. The maintenance phase was extended to 30 months with additional intensifications owing to late relapses after completion of POMP therapy. Newly diagnosed or primary refractory (1 course only) pts with ALL (n=204) or LL (n=27) were treated on the two sequential studies. Burkitt-type leukemia/lymphoma (BLL) and Philadelphia positive ALL were treated on alternative protocols. From May 2000 to December 2001, 69 pts were treated with modified hyper-CVAD with anthracycline intensification (9 induction-consolidation courses). Course 2 was then eliminated from the regimen (8 courses), with an additional 162 pts treated to date (pts age 30 years or less are now treated with augmented BFM). Median age was 43 yrs (range, 15–83). CD20 expression was noted in 49%. Overall CR rate of the evaluable group (n=225) was 93%; 7 pts achieved PR (LL with residual disease), five failed to respond, and 4 died during the induction phase. Three-yr CRD and OS rates were 70% and 62%, respectively after a median follow-up of 50 months (range, 2–106+). In the younger CD20 positive precursor B-cell ALL subset (n=99), rituximab improved outcome compared to historical experience with hyper-CVAD alone (n=127), with 3-yr CRD rates (75% vs 45%, p<.001) and OS rates (65% vs 38%, p<.001) approaching those of their CD20 negative counterparts. In contrast to the Burkitt experience, rituximab was not beneficial for the elderly subgroup (OS rates 28% vs 34%, p NS). Anthracycline intensification did not improve outcome. The addition of rituximab to the hyper-CVAD regimen appears to benefit the younger pts (age less than 60 yrs) with CD20 positive precursor B-cell ALL. Incorporation of rituximab and other monoclonal antibodies (e.g., ofatumumab, epratuzumab) into frontline chemotherapy regimens for ALL should be investigated systematically. Disclosures: No relevant conflicts of interest to declare.

A Brief Use of Imatinib Immediately Before Hematopoietic Stem Cell Transplantation (HSCT) in Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL). Results of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph+ALL04

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2554-2554
Author(s):  
Atsushi Manabe ◽  
Hirohide Kawasaki ◽  
Motoaki Chin ◽  
Atsushi Sato ◽  
Kimikazu Matsumoto ◽  
...  
Keyword(s):  
Survival Rate ◽  
Medical Information ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
High Dose ◽  
Induction Phase ◽  
Study Group ◽  
Pediatric Leukemia ◽  
Hematopoietic Stem

Abstract Abstract 2554 Aims: Children with Ph+ALL generally have a poor prognosis when treated with chemotherapy alone. The timing and duration of the use of imatinib has not been determined. We investigated a role of imatinib immediately before HSCT. Methods: All the patients with ALL were screened for diagnosis of Ph+ALL using RT-PCR. Children with Ph+ALL were enrolled on JPLSG Ph+ALL04 Study within 1 week of initiation of treatment for ALL. Treatment regimen consisted of 5 therapeutic phases: Induction phase (5-drug induction), Intensification phase (high-dose cytarabine and BFM Ib), Re-induction phase (4-drug re-induction), 2 weeks of Imatinib monotherapy phase (23 weeks after diagnosis), and HSCT phase (Etoposide+CY+TBI conditioning). Before and after each phase, minimal residual disease (MRD), the amount of BCR-ABL transcripts, was measured with the real-time PCR method (cut-off 50 copies/microgram RNA). The study was registered in UMIN-CTR (Medical Information, University hospital Medical Information Network - Clinical Trials Registry): UMIN ID C000000290. Results: During the period 2004–08, 42 patients were registered in the Ph+ALL04 study. Out of 42 patients, 37 patients (88%) achieved CR and 7 of 37 patients also achieved MRD-negative after induction phase. There were 13 patients who had no MRD at the beginning of imatinib monotherapy phase, and 14 patients were MRD-negative after imatinib phase, consequently, 14 patients were MRD-negative at the time of HSCT. Six patients relapsed before HSCT. In total, 31 patients received HSCT in 1st CR. All the patients had engraftment and no patients died because of complications of HSCT. Five patients relapsed after HSCT and 4 of the 5 patients were MRD-negative before HSCT and the other patient had detectable MRD although it was less than 50 copies. Twenty-six patients continue to be in 1st CR and MRD-negative for median of 3 years after diagnosis. The 3-year event-free survival rate and over-all survival rate for all the patients was 57% and 80%, respectively (figure 1). Five patients did not achieve CR after induction phase and they were treated with imatinib-contained chemotherapy. Four of the 5 patients achieved CR. All of the 4 patients received cord blood transplantation and remains in continued CR. Interpretation: The chemotherapy we employed was based on the previous high-risk regimen of TCCSG (Tokyo Children's Cancer Study Group) L-99-15 Study. The chemotherapy was intensive enough to induce MRD-negative in 13 at the time of imatinib phase and 31 of 42 patients were in CR at the time of HSCT (around 25–28 weeks after diagnosis). We planned to assess the efficacy of imatinib immediately before HSCT but it was not possible because of the low amount of MRD in most patients at the beginning of imatinib phase. Conclusion: Although EFS and OS was excellent in this study, 88% of induction rate appeared unsatisfactory and relapse occurred before HSCT in 6 out of 37 patients who achieved CR after induction phase. Earlier and longer use of imatinib may improve EFS in children with Ph+ALL and HSCT may be omitted in a subset of patients who achieve an early and deep remission status. Disclosures: No relevant conflicts of interest to declare.

De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1240-1247 ◽  
Author(s):  
Thierry Dervieux ◽  
Timothy L. Brenner ◽  
Yuen Y. Hon ◽  
Yinmei Zhou ◽  
Michael L. Hancock ◽  
...  
Keyword(s):  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Initial Therapy ◽  
High Dose ◽  
Purine Synthesis ◽  
Percentage Decrease ◽  
Before And After ◽  
Leukocyte Counts ◽  
B Lineage

Methotrexate (MTX) and mercaptopurine (MP) are widely used antileukemic agents that inhibit de novo purine synthesis (DNPS) as a mechanism of their antileukemic effects. To elucidate pharmacodynamic differences among children with acute lymphoblastic leukemia (ALL), DNPS was measured in leukemic blasts from newly diagnosed patients before and after therapy with these agents. Patients were randomized to receive low-dose MTX (LDMTX: 6 oral doses of 30 mg/m2) or high-dose MTX (HDMTX: intravenous 1 g/m2) followed by intravenous MP; or intravenous MP alone (1 g/m2), as initial therapy. At diagnosis, the rate of DNPS in bone marrow leukemia cells was 3-fold higher in patients with T-lineage ALL compared with those with B-lineage ALL (769 ± 189 vs 250 ± 38 fmol/nmol/h;P = .001). DNPS was not consistently inhibited following MP alone but was markedly inhibited following MTX plus MP (median decrease 3% vs 94%; P &lt; .001). LDMTX plus MP and HDMTX plus MP produced greater antileukemic effects (percentage decrease in circulating leukocyte counts) compared with MP alone (−50% ± 4%, −56% ± 3%, and − 20% ± 4%, respectively;P &lt; .0001). Full DNPS inhibition was associated with greater antileukemic effects compared with partial or no inhibition (−63% ± 4% vs −37% ± 4%; P &lt; .0001) in patients with nonhyperdiploid B-lineage and T-lineage ALL. HDMTX plus MP yielded 2-fold higher MTX polyglutamate concentrations than LDMTX plus MP (2148 ± 298 vs 1075 ± 114 pmol/109 cells;P &lt; .01) and a higher percentage of patients with full DNPS inhibition (78% vs 53%; P &lt; .001). Thus, the extent of DNPS inhibition was related to in vivo antileukemic effects, and a single dose of intravenous MP produced minimal DNPS inhibition and antileukemic effects, whereas MTX plus MP produced greater antileukemic effects and DNPS inhibition, with full inhibition more frequent after HDMTX.

scholarly journals ANALYSIS OF INDUCTION PHASE GLUCOCORTICOID USE ON ADRENAL SUPPRESSION IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2017 ◽  
Vol 52 (1) ◽  
pp. 7
Author(s):  
Octaviana Simbolon ◽  
Yulistiani Yulistiani ◽  
I DG Ugrasena ◽  
Mariyatul Qibtiyah
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
High Risk Group ◽  
Adrenal Suppression ◽  
Induction Phase ◽  
Childhood All ◽  
Cortisol Levels ◽  
Standard Risk

Glucocorticoids play an important role in the treatment of acute lymphoblastic leukemia (ALL). However, supraphysiological doses may cause suppression of the adrenal. Adrenal suppression resulting in reduced cortisol response may cause an inadequate host defence against infections, which remains a cause of morbidity and mortality in children with ALL. The occurrence of adrenal suppression before and after glucocorticoid therapy for childhood ALL is unclear. The aim of this study is to analysis the effect of glucocorticoid on cortisol levels during induction phase chemotherapy in children with acute lymphoblastic leukemia. A cross-sectional, observational prospective study was conducted to determine the effect of glucocorticoid on cortisol levels in children with acute lymphoblastic leukemia. Patients who met inclusion criteria were given dexamethasone or prednisone therapy for 49 days according to the 2013 Indonesian Chemotherapy ALL Protocol. Cortisol levels were measured on days 0, 14, 28, 42 and 56 of induction phase chemotherapy. There were 24 children, among 31 children recruited, who suffered from acute lymphoblastic leukemia. Before treatment, the means of cortisol levels were 228.95 ng/ml in standard risk group (prednisone) and 199.67 ng/ml in high risk group (dexamethasone). In standard risk group, the adrenal suppression occurs at about day 56. There was a significant decrement of cortisol levels in high risk group in days 14, 28, 42 against days 0 of induction phase (p=0.001). Both groups displayed different peak cortisol levels after 6 week of induction phase (p=0.028). Dexamethasone resulted in lower cortisol levels than prednisone during induction phase chemotherapy in children with acute lymphoblastic leukemia.

scholarly journals Rats Lacking Dopamine Transporter Display Increased Vulnerability and Aberrant Autonomic Response to Acute Stress

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 842
Author(s):  
Placido Illiano ◽  
Gregory E. Bigford ◽  
Raul R. Gainetdinov ◽  
Marta Pardo
Keyword(s):  
Dopamine Transporter ◽  
Hpa Axis ◽  
Acute Stress ◽  
Female Rats ◽  
Autonomic Response ◽  
Before And After ◽  
Response To Stress ◽  
Vulnerability To Stress ◽  
Body Temperature Increase ◽  
Reduced Temperature

The activity of the hypothalamus–pituitary–adrenal (HPA) axis is pivotal in homeostasis and presides the adaptative response to stress. Dopamine Transporter (DAT) plays a key role in the regulation of the HPA axis. We used young adult female DAT Knockout (KO) rats to assess the effects of DAT ablation (partial, heterozygous DAT+/-, or total, homozygous DAT-/-) on vulnerability to stress. DAT-/- rats show profound dysregulation of pituitary homeostasis, in the presence of elevated peripheral corticosterone, before and after acute restraint stress. During stress, DAT-/- rats show abnormal autonomic response at either respiratory and cardiovascular level, and delayed body temperature increase. DAT+/- rats display minor changes of hypophyseal homeostatic mechanisms. These rats display a similar pituitary activation to that of the control animals, albeit in the presence of higher release of peripheral corticosterone than DAT-/- after stress, and reduced temperature during stress. Our data indicate that DAT regulates the HPA axis at both the central and peripheral level, including autonomic function during stress. In particular, the partial deletion of DAT results in increased vulnerability to stress in female rats, which display central and peripheral alterations that are reminiscent of PTSD, and they might provide new insights in the pathophysiology of this disorder.

Intensified Chemotherapy Regimen for Very High Risk Childhood B-Precursor Acute Lymphoblastic Leukemia (B-ALL): Results From Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05–01

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3563-3563
Author(s):  
Lynda M. Vrooman ◽  
Kristen E. Stevenson ◽  
Marian Harris ◽  
Donna S. Neuberg ◽  
Stephen E. Sallan ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Total Duration ◽  
Pcr Analysis ◽  
High Dose ◽  
Induction Phase ◽  
Cell Transplant ◽  
Very High

Abstract Abstract 3563 Background: High levels of minimal residual disease (MRD) at the end of 4-weeks of multiagent induction chemotherapy have been shown to be associated with a high risk of subsequent relapse in pediatric patients (pts) with B-ALL. Published reports indicated that pediatric B-ALL pts with high end-induction MRD had event-free survival (EFS) rates < 50% when treated with standard chemotherapy.[Zhou, Blood 2007; Borowitz Blood 2008] Pts with high-risk (HR) cytogenetic abnormalities, such as low hypodiploidy and MLL gene rearrangements (MLL-R) also have a high relapse risk. On DFCI ALL Consortium Protocol 05–01, we piloted an intensified regimen for B-ALL pts with high end-induction MRD and/or HR cytogenetics. Methods: Between 2005–2010, 482 evaluable pts aged 1–18 years with B-ALL were enrolled. Pts were initially classified as standard-risk (SR) or high-risk (HR) based on NCI age/WBC criteria. MRD was prospectively evaluated at the end of the 4-week induction phase via RQ-PCR analysis of IgH or TCR rearrangements. Results were reported as the ratio of copy numbers of target gene:GAPDH; a ratio >0.001 was considered high MRD. Pts with high MRD or HR cytogenetics (hypodiploidy with <45 chromosomes or MLL-R) were reclassified at the end of induction phase as very high risk (VHR), and received 2 additional chemotherapy cycles beginning at week 7 (cycle 1: cyclophosphamide, low-dose cytarabine, 6-MP; cycle 2: high-dose cytarabine, etoposide, dexamethasone, L-asparaginase), followed by the DFCI ALL Consortium HR consolidation phase, including 30 weeks of L-asparaginase and doxorubicin to a cumulative dose of 300 mg/m2. After consolidation, pts received a standard maintenance phase. Total duration of treatment was 25 months. Results: 51 pts (11%) were classified as VHR, 25 of whom had been initially classified as SR and 26 as HR. 35 VHR pts had high end-induction MRD as the sole VHR criterion; 16 had HR cytogenetics. 9 pts relapsed (all marrow-involved) and 1 pt developed a secondary AML. There were no deaths in first remission. With median follow-up of 4.4 yrs, the 5-yr EFS (95% confidence interval) for all 51 VHR pts was 76% (60,87)[Figure 1] and 5-yr overall survival was 81% (60,92). The 5-yr EFS was 81% (59,90) for the 35 pts with high MRD. Conclusion: Intensification of chemotherapy (without stem cell transplant) resulted in a relatively favorable EFS in VHR B-ALL pts (defined by the presence of either high end-induction MRD or HR cytogenetics). More pts and longer follow-up will be necessary to confirm these promising results. Disclosures: No relevant conflicts of interest to declare.

Outcome of 136 Children with Advanced Lymphoblastic Lymphoma Receiving an BFM-Type Therapy with Intensified Maintenance: A Report from the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3049-3049
Author(s):  
Shosuke Sunami ◽  
Masahiro Sekimizu ◽  
Tetsuya Takimoto ◽  
Tetsuya Mori ◽  
Tetsuo Mitsui ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Lymphoblastic Lymphoma ◽  
High Dose ◽  
Induction Phase ◽  
Pediatric Leukemia ◽  
Cns Disease ◽  
Stage 4 ◽  
Mediastinal Disease ◽  
Significant Difference

Abstract BACKGROUND: Lymphoblastic lymphoma (LBL) accounts for 30% of childhood non Hodgkin’s lymphoma in Japan. From European and North American groups, favorable results have been reported, using treatment strategies for acute lymphoblastic leukemia, over 80% of event free survival rate even in advanced LBL. However there were few data on Japanese or Asian patients with LBL. Here we report final outcome of first nation-wide prospective study over one hundred cases with advanced childhood LBL from Japan. PATIENTS & METHOD: Patients with stage 3 or 4 LBL received for 9 weeks induction phase, which consisted of 7 drugs and triple IT , followed by three courses of high dose MTX(5g/m2). After high dose MTX, re-induction, early maintenance, and late maintenance phase were administered. With an attempt to intensify maintenance therapy,early maintenance was consisted by two cycles of four courses of six drugs(MTX, PSL,VCR, L-ASP, 6MP, THP#) and late maintenance was five cycles of five drugs(MTX, PSL,VCR, 6MP,AraC). We omitted local radiotherapy including prophylactic cranial radiotherapy except patient with initial central nervous system (CNS) disease. The total duration of the treatment was 24 month‚“. RESULTS: From November 2004 to October 2010, 154 children with newly diagnosed advanced stage LBL were entered in this study. A total of 136 cases were eligible. Ages ranged from four month to 15 years, with a median of 9.07 years. Of the 136 patients, 36 were girls and 100 were boys. The distribution of clinical stage 3 and stage 4 was 82 and 54 patients respectively. 94 patients had primary mediastinal disease. 41 patients had BM disease, 31 patients had CNS disease and 8 patients had BM and CNS disease. 104 patients (76.5%) had precursor T LBL (T-LBL), 31 patients (22.8%) had precursor B LBL (B-LBL), onepatient (0.7%) had bi phenotype LBL. The follow-up time ranged from 2.8 to 94 months, with a median 58 months. For the 136 patients analyzed in this study, 5-year OS was 82.9% and 5-year EFS was 77.9%. There was no significant difference in outcome by gender (5-year EFS, male 78.2% vs. female 73.0%), or by immunophenotype (5-year EFS, B-LBL 80.7% vs. T-LBL 76.9%). Of note, the 5-year EFS for stage 3 T-LBL patients were worse than that of stage 4 T-LBL patients (70.6% vs. 88.9%, P=0.031). There were also significant difference in 5-year EFS for T-LBL patients who achieved CR and CRu at end of induction, 86.9%, and 69.7% (P=0.034), respectively.Most events were observed as mediastinum enlargement before initiation of intensified maintenance therapy. CONCLUSIONS: Our firstnationwide study provided about 80% cure rate with only one case of toxic death in childhood advanced LBL. However, our intensified maintenance therapy could not improve survival outcome. Our result also emphasize the significant difference between T-LBL stage 3 and stage 4 and might suggest the difference in ethnicity for the composition of biological subgroup in T-LBL. THP: Pirarubicin Disclosures No relevant conflicts of interest to declare.

Incidence of Adrenal Insufficiency in Patients with Multiple Myeloma during High Dose Chemotherapy and Autologous Stem Cell Transplant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5862-5862 ◽  
Author(s):  
Ahmad Hatem Mattour ◽  
Shatha Farhan ◽  
Nalini Janakiraman ◽  
Edward Peres
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Adrenal Insufficiency ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Adrenal Function ◽  
High Dose ◽  
Cell Transplant ◽  
Cortisol Levels

Abstract Background High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is considered the standard of care for patients with multiple myeloma (MM). With most patients receiving induction therapy that includes corticosteroids. The combined effect of prior therapy for myeloma and ASCT related complications may result in hypotension and require intensive medical treatment. To date the incidence of adrenal insufficiency in the setting of ASCT is unknown. The effects of this underlying disorder in regards to post transplant outcome remain unknown as well. We set out to compare the outcomes of patients with multiple myeloma who underwent ASCT with adrenal insufficiency compared to those with sufficient adrenal function. Methods We undertook a prospective study in 13 consecutive patients with Multiple Myeloma admitted for high dose chemotherapy and autologous stem cell transplant at Henry Ford Hospital between February 2014 through June 2014, with the first patient sample being obtained in on 2/14/2014 and last sample recorded in 6/23/2014. Random cortisol levels were obtained on the day of admission or day -2 (figure 1), prior to the start of high dose chemotherapy. All prior therapies included corticosteroids and consisted of the following RVD, DCEP, RD, VD, DT-PACE. Patients were classified into two groups those with cortisol levels > 5 and those patients who had cortisol levels <5. Endpoints analyzed included hypotension, septic shock, and duration of antibiotic therapy. Results Of the 13 patients analyzed the median age was 60 years old (range 53-78), gender 8 male patients 5 female. All patients underwent high dose chemotherapy with Melphalan and Autologous stem cell transplant. Of the 13 patients in which data was obtained 3/13 23% had adrenal insufficiency prior to high dose Melphalan and ASCT. With a median cortisol level of 3.2 in the patient cohort who were found to be adrenal insufficient. The incidence of hypotension was 2/3 66% in the adrenal insufficient patients compared 1/10 10% in the cohort with sufficient adrenal function. Septic shock occurred in 2/3 66% of the adrenal insufficient compared to 0/10 in the adrenal sufficient group. The median duration of antibiotic therapy was 5 days in the adrenal insufficient cohort compared to 2 days in the patients with adequate adrenal function. Conclusion In this small cohort of consecutive patients from a single center, we found that there was a high incidence of adrenal insufficiency 23% in patients undergoing ASCT. The treatment regimens varied in the study group with all patients receiving corticosteroid therapy in there induction regimen. Given the unexpectedly high incidence of adrenal insufficiency a consideration should be given to check a random cortisol level prior to the initiation of HDC. Supplemental therapy or treatment should be considered in this high risk group to avoid unnecessary complications and prolonged antibiotic use and supportive care in this patient cohort. Figure 1. Random Cortisol levels obtained prior to Autologous stem cell transplant Figure 1. Random Cortisol levels obtained prior to Autologous stem cell transplant Disclosures No relevant conflicts of interest to declare.

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