Impact of Day 28 Absolute Lymphocyte Count On Outcome of Hematopoietic Cell Transplant (HCT) in CR1 for Adult Patients with Acute Lymphoblastic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1472-1472 ◽  
Author(s):  
Jonathan A Rose ◽  
Tamara J. Dunn ◽  
Michaela Liedtke ◽  
Paul Elson ◽  
Matt Kalaycio ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphocyte Count ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Multivariable Analysis ◽  
Absolute Lymphocyte Count ◽  
Newly Diagnosed ◽  
Univariable Analysis ◽  
Median Interval

Abstract Abstract 1472 Introduction: Despite significant advances in survival rates for pediatric Acute Lymphoblastic Leukemia (ALL) patients (pts), long-term survival rates for adults with ALL have remained below 40%. An absolute lymphocyte count (ALC) < 350/μL at Day 28 of induction therapy is predictive of poor outcome [event-free survival (EFS) and overall survival (OS)] in adults with newly diagnosed ALL. It is unknown, however, whether ALC at Day 28 is also predictive of outcome in those patients who undergo allogeneic HCT in CR1. We hypothesized that the prognostic impact of ALC at Day 28 might be nullified by HCT in CR1 due to the graft versus leukemia effect. Methods: We conducted a retrospective chart review of 90 adult pts (≥ 18 yrs of age) with de novo ALL who underwent HCT while in CR1 during the years 1998–2011 at the Cleveland Clinic and Stanford, 66 of whom were evaluable for data analysis. Institutional review board approval was obtained at each institution. Prior studies identified an ALC of 350/ μL at Day 28 of induction therapy as a cut-off predictive of outcome. Therefore, we evaluated this number as well as other cut-offs. Cytogenetic (CG) risk was ascribed by CALGB criteria. We also evaluated the impact of gender, age at diagnosis, CG, and WBC at diagnosis. The Kaplan-Meier method was used to summarize OS and EFS, which were measured from HCT to death and the first of relapse/death, respectively. The log-rank test was used for univariable analysis of categorical factors and the Cox proportional hazards model, stratified by institution, was used for multivariable analysis and univariable analysis of measured factors. Patient characteristics: Median age: 38 yrs (range 19–66); Gender: 58% (38) male; CG risk: 57 (86%) poor, 5 (8%) miscellaneous, 4 (6%) normal; 64 (97%) B-cell lineage; median WBC at diagnosis 18.1 K/μL (range 0.9–432); median Day 28 ALC 440/μL (range 0–2450). The majority of pts (50, 76%) received a vincristine/prednisone/anthracycline-based induction regimen, with the remainder receiving a high-dose cytarabine based regimen. The median interval between the start of induction and CR was 28 days and the median interval from CR to HCT was 3.2 months (0.2–10.8). Results: Median EFS and OS have not been reached; 1-year EFS is estimated to be 57% ± 6%, and 2-year OS 57% ± 7%. In univariable analyses age > 50 (EFS) and WBC at diagnosis ≥ 40 K/μL (EFS and OS) were associated with worse outcomes (all p ≤ 0.04). A Day 28 ALC < 250/μL (but not < 350/μL) was also associated with decreased EFS [HR 2.27 (1.08–4.79), p=0.03] (Figure 1) with a trend towards worse OS [HR 1.89 (0.89–4.04), p=0.10]. WBC and Day 28 ALC remained statistically significant prognostic factors for RFS on multivariable analysis; HRs 2.89 (1.38–6.05), p=0.005 and 2.25 (1.06–4.78), p=0.04, respectively. Conclusion: ALC at Day 28 remains prognostic for outcome in newly diagnosed ALL pts undergoing HCT in CR1. Further characterization of the lymphocytes in pts with high ALCs and their potential role in preventing relapse is needed. Disclosures: No relevant conflicts of interest to declare.

Triple Intrathecal Therapy Alone With Omission of Cranial Radiation in Children With Acute Lymphoblastic Leukemia

2014 ◽  
Vol 32 (17) ◽  
pp. 1825-1829 ◽  
Author(s):  
Hsi-Che Liu ◽  
Ting-Chi Yeh ◽  
Jen-Yin Hou ◽  
Kuan-Hao Chen ◽  
Ting-Huan Huang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Cumulative Risk ◽  
Cranial Irradiation ◽  
Intrathecal Therapy ◽  
Newly Diagnosed ◽  
Cns Relapse ◽  
Risk Patients ◽  
A Prospective Study

Purpose To eliminate the toxicities and sequelae of cranial irradiation (CrRT) and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, a prospective study of a modified CNS-directed therapy was conducted in children with acute lymphoblastic leukemia (ALL). Patients and Methods Since June 1999, children with newly diagnosed ALL have been treated with triple intrathecal therapy (TIT) alone without CrRT. The first TIT was delayed until the disappearance of blasts from peripheral blood (PB) for up to 10 days of multidrug induction, and CrRT was omitted in all patients. If PB blasts persisted on treatment day 10 (d10), the TIT was then performed. Results Of a total of 156 patients, 152 were eligible. Seventeen patients did not have PB blasts at diagnosis. Three fourths of the remaining patients achieved complete clearance of PB blasts by d10. Only hyperleukocytosis at diagnosis showed a significantly lower clearance rate. Six standard-risk patients were upgraded to high risk because of detectable PB blasts on d10. TLPs were encountered in four patients (2.6%), but none were contaminated with lymphoblasts. Neither CNS-2 (less than 5 WBCs/μL with blasts in a nontraumatic sample) nor CNS-3 (≥ 5 WBCs/μL with blasts in a nontraumatic sample or the presence of cranial nerve palsy) was present. The 5-year event-free survival and overall survival rates ± SE were 84.2% ± 3.0% and 90.6% ± 2.4%, respectively. No isolated CNS relapse occurred, but two patients experienced combined CNS relapses. The 7-year cumulative risk of any CNS relapse was 1.4% ± 1.0%. Conclusion Delaying first TIT until circulating blasts have cleared may improve CNS control in children with newly diagnosed ALL and preclude the need for CrRT.

Dexamethasone and Individualized Asparaginase Dosing Are Each Associated with Superior Event-Free Survival in Childhood Acute Lymphoblastic Leukemia: Results From DFCI-ALL Consortium Protocol 00-01.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 321-321 ◽  
Author(s):  
Lynda M. Vrooman ◽  
Donna S. Neuberg ◽  
Kristen E. Stevenson ◽  
Jeffrey G. Supko ◽  
Stephen E. Sallan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Multivariable Analysis ◽  
Hazard Ratio ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
To Receive

Abstract Abstract 321 BACKGROUND: The DFCI-ALL Consortium Protocol 00-01 aimed to determine the relative efficacy and toxicity of 1) dexamethasone (DEX) vs. prednisone (PRED) and 2) asparaginase (ASP) with individualized dosing (ID) based on pharmacokinetic measurements vs. standard fixed dosing (FD) based on body surface area, in the treatment of children with newly diagnosed acute lymphoblastic leukemia (ALL). PATIENTS and METHODS: Between 2000 and 2004, 492 eligible patients (pts) ages 1-18 years (yrs) with newly diagnosed ALL enrolled on Protocol 00-01 from 10 institutions. 282 pts were standard risk (SR) and 210 high risk (HR). Post-induction treatment for all patients included 30 weeks of intramuscular E. coli ASP (beginning at week 7) and vincristine/corticosteroid pulses every 3 weeks for 24 months. Pts who achieved complete remission (CR) were eligible for two randomized comparisons: 1) Steroids: Pts were randomized to receive either DEX or PRED given as 5-day pulses every 3-weeks, and 2) ASP: Pts were randomized to receive either FD (25,000IU/m2) or ID (starting dose 12,500 IU/m2) for 30 weeks. Nadir serum ASP activity (NSAA) was assessed every 3 weeks, and ASP doses on the ID arm were adjusted to maintain NSAA between 0.10-0.14 IU/mL. NSAA was assayed centrally by a validated biochemical assay. RESULTS: 473 pts (96%) achieved CR. With a median follow-up of 4.9 years, the 5-year event-free survival (EFS) ± standard error for all 492 pts was 80 ± 2% and overall survival (OS) was 91 ± 1%. Steroid randomization: 408/473 pts (86%) participated in the steroid randomization (DEX: 201, PRED: 207). Pts randomized to DEX had 5-yr EFS of 90 ± 2% compared with 81 ± 3% for PRED (p=0.01) [Table I]. For pts 10-18 yrs of age, there was a significant increase in the rate of osteonecrosis (ON) with DEX, with 5-yr cumulative incidence (CI) of 23% compared with 4.7% for PRED (p=0.02). There was no difference in the 5-yr CI of ON based on steroid type in pts 1-10 yrs of age (DEX: 2.6% vs. PRED: 4.3%, p=0.43). Fractures were also more common in pts 10-18 yrs of age randomized to DEX (p=0.06), but not in younger pts (p=0.25). Infection (positive blood culture or radiographic evidence of invasive fungal disease) developed in 38 pts (18.8%) randomized to DEX compared with 22 pts (10.6%) randomized to PRED (p=0.03). There was no difference in remission death rate based on steroid randomization (DEX 0% vs. PRED 2%, p=0.5). ASP randomization: 384/473 pts (81%) participated in the ASP randomization (FD: 195, ID: 189). Pts randomized to ID had superior EFS with 5-yr EFS of 90 ± 2% compared with 82 ± 3% for FD (p=0.04) [Table I]. There was no difference between the two arms in the frequency of ASP-related allergy (p=0.46), pancreatitis (p=0.66) or thrombosis (p=0.77). There was also no difference by treatment arm in the proportion of pts able to complete at least 25 weeks of ASP (FD: 88% vs. ID: 87%, p=0.76). There was no difference between the two arms in the proportion of pts with non-detectable NSAA, although fewer pts on the ID arm had high NSAA (>0.14 IU/mL). On multivariable analysis, both DEX and ID ASP were independent predictors of favorable outcome (hazard ratio 0.49 for DEX, p=0.02; hazard ratio 0.52 for ID, p=0.04), with no indication of an interaction. Only 5/92 (5%) pts randomized to both DEX and ID ASP experienced an event. CONCLUSIONS: DEX was associated with superior EFS, but also more bone and infectious toxicities, especially in older children/adolescents. Future studies should focus on minimizing DEX toxicity in older pediatric pts without compromising efficacy. ID of ASP was feasible and was associated with superior EFS. The improved EFS with ID was not due to a reduction in ASP-related toxicity or improved tolerability, but was associated with a reduction in the proportion of pts with high NSAA. Disclosures: Supko: Enzon Inc.: Research Funding. Sallan:Enzon Inc.: Research Funding; Enzon Inc.: Contributed to support of an investigator meeting.

Infectious Central Venous Line Complications During Induction Therapy for Newly Diagnosed Acute Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4322-4322
Author(s):  
Rebecca Cook ◽  
Roger Berkow
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Wound Dehiscence ◽  
Newly Diagnosed ◽  
Central Venous ◽  
Central Lines ◽  
Picc Line

Abstract Abstract 4322 Introduction: Childhood acute leukemia treatment requires central venous lines (CVL) for instillation of chemotherapy and blood products. Ideally, a proper white cell count (WBC) and absolute neutrophil count (ANC) ensure proper healing of CVLs, but this is challenging in children with acute leukemia. We sought to investigate the CVL complication rate in newly diagnosed children with acute leukemia during their induction therapy, and determine if the degree of neutropenia at the time of CVL placement correlated with the number of CVLs lost due to infection, wound dehiscence, or thrombosis. Methods: We conducted a retrospective chart review of children diagnosed with leukemia between January 2007 and December 2009 and recorded leukemia type, WBC and ANC at diagnosis and at the time of CVL placement, the type of CVL placed (external line, subcutaneous port) or placement of peripherally inserted central (PICC) line. We recorded complications, including infection, line malfunction, wound dehiscence, and thrombosis within their induction therapy phase. Results: Ninety-five children were evaluable, including 68 children with precursor B acute lymphoblastic leukemia (pre B ALL), 19 with acute myelogenous leukemia (AML), and 8 with T-cell acute lymphoblastic leukemia (T cell ALL). Ninety-eight CVLs were placed in 94 children (1 child died of complications of APML before initiation of therapy). There were 77 subcutaneous ports and 21 external lines placed. Eleven patients received PICC lines for various reasons (ex – sedation risk due to large mediastinal mass or altered mental status due to leukocytosis, coagulopathy, refractory thrombocytopenia, previously placed PICC line at outside hospital). ANC at the time of CVL insertion was reviewed: ANC<500 in 39 central lines, 500–1000 in 29 central lines, and >1000 in 30 central lines. Only 1 central line was removed due to wound dehiscence in a child with T cell ALL, and 2 central lines were removed for cellulitis in children with pre B ALL, and all these patients had ANC<500 at the time of line insertion. Two of the 98 central lines developed an associated thrombosis (1 CVL associated extensive arm venous thrombus and 1 external line with small atrial thrombus at tip of catheter), as opposed to 2 of the 11 PICC lines placed (both extensive arm venous thrombi). Seventeen positive blood cultures occurred during the first month of induction (15 from central lines and 2 from PICC lines), and all infections cleared with antibiotics except for 1 patient with PICC-associated venous thrombosis and persistent MRSA bacteremia. One subcutaneous port had to be revised after 3 days due to deep insertion and difficultly accessing; this child had ANCs<500 during each surgery and healed without complications. Three external lines were removed due to malfunction (2 with ANC<500, 1 with ANC 500–1000 at time of insertion). Conclusions: Nearly 40% of CVLs were placed in times of severe neutropenia (ANC<500), and only 3 were lost due to cellulitis or wound dehiscence. No CVL was lost due to persistent bacteremia compared to 1 PICC line. There was an increased incidence of thrombosis in PICC lines (2 of 11 placed) compared to external lines or ports (2 of 98 lines placed). We failed to see an increased risk of infection due to degree of neutropenia at the time of CVL insertion. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effectiveness of Dexamethasone compared with Prednisolone in Induction Therapy of Childhood Acute Lymphoblastic Leukemia

2016 ◽  
Vol 6 (1) ◽  
pp. 3-9
Author(s):  
Tofazzal Hossain ◽  
MA Mannan ◽  
Shamsoon Nahar ◽  
AKM Amirul Morshed ◽  
Shahnoor Islam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Group A ◽  
Bone Marrow Study ◽  
Group B

Background: Corticosteroids are an essential component of treatment for acute lymphoblastic leukemia (ALL). Prednisolone is the most commonly used steroid. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of central nervous system compared with prednisolone.Objectives: To determine the effect of dexamethasone and prednisolone and to compare them in induction therapy of ALL in Children.Material & Methods: A total of 60 newly diagnosed cases of ALL confirmed by bone marrow study, children of either sex with age >1 year were included in this study. Variables studied were age, sex, presenting features, neutrophil count, blast cell count, platelet count, bone marrow status at diagnosis, on D15 & D29 of induction and side effects.Results: Mean age of the patients of group A was 6.28 years & that of group B was 7.2 years. Out of all patients of group A 19 (63.3%) were male and 11 (36.7%) were female. In group B 21 (70.0%) patients were male and rests 9 (30.3%) were female. No statistically significant difference was observed in both groups in terms of age, sex & presenting features. After induction significant difference was observed in liver & spleen size at day 7 and day 15. All patients of both groups had M3 marrow status at diagnosis. Overall, in group A 93.3% patients achieved M1 marrow status (fewer than 5% blasts) and 6.7% had M2 marrow status (5-25% blasts) at day 15 of induction. On the other side 66.7% patients of group B achieved M1 status and 33.3% M2 status at day 15. Statistically significant difference was observed between groups on day 15 in term of achieved marrow status (p<0.05). No statistically significant difference was observed between groups in term of infection in difference days of induction. On day 16 of induction maximum incidence of infection was observed in both groups.Conclusion: Dexamethasone may be an effective alternative option to prednisolone for the treatment of acute lymphoblastic leukemia in children.J. Paediatr. Surg. Bangladesh 6(1): 3-9, 2015 (Jan)

Lack of Prognostic Significance of Absolute Lymphocyte Count After Intensive Induction Therapy in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4909-4909
Author(s):  
Khaldoun J. Alkayed ◽  
Faris Madant ◽  
Abdulla Ibrahim ◽  
Hadeel Halasheh ◽  
Eman Khattab ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Lymphocyte Count ◽  
Prognostic Value ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Absolute Lymphocyte Count ◽  
Prognostic Effect ◽  
Post Induction

Abstract Abstract 4909 Introduction: Previous work has shown that the function and number of lymphocytes are vital for the patient's immune system to mount an effective response against cancer cells. Multiple recent studies have demonstrated the prognostic value of absolute lymphocyte count (ALC) in a wide range of malignancies. In children with acute lymphoblastic leukemia (ALL), ALC during induction chemotherapy have been shown to be an independent predictor of adverse outcome, even in the era of minimal residual disease (MRD). Most of the previous studies used Children Oncology Group (COG) based regimens with 3 or 4 drugs induction. We hypothesized that with more intensive induction regimens with 5 or 7 drugs, ALC would lose its prognostic value due to more intensive chemotherapy induced leukopenia. Patients/methods: We reviewed 136 Jordanian pediatric patients (Arabic ethnicity) with newly diagnosed ALL, age 1–18 years, from 2007 to 2009. The patients were treated at a single institution on modified St. Jude total XIII and VX protocols, with a median follow up of 35 months (range: 2–54 months). The induction phase was composed of 7 drugs regimen. Variables analyzed included ALC at diagnosis, day15, day 36 end of induction chemotherapy and at time of post induction marrow recovery, white blood cells at diagnosis, age at diagnosis, gender, immunophenotype, cytogenetics, risk group and MRD status at end of induction. ALC at each time-point was evaluated for prognostic ability by univariate and multivariate analysis. Results: We found that ALC at day15, day 36 end of induction chemotherapy and at time of post induction marrow recovery failed to have any prognostic effect on event-free survival (EFS) or overall survival (OS). We analyzed ALC as continuous and dichomatous variable, but without any prognostic significance. In contrast to our hypothesis, children with ALL intensive induction regimen did not have profound lymphopenia, with ALC day15 median of 1260 cells/ml (range: 0–9450), ALC day36 median of 866 (range: 100–3476), and ALC (post induction marrow recovery) median of 1145 cells/ml (range: 85–9676). Our cohort confirmed several known prognostic factors in childhhod ALL. For EFS outcome we found MRD35, age, phenotype and risk group to have a significant prognostic effect with P values of (0.016, 0.005, 0.006, 0.001) respectively. For OS outcome we found both age and phenotype to have a significant prognostic P value of (0.006 and <0.001) respectively. Conclusions: In this study we failed to replicate the previous work that showed the independent prognostic value of ALC during induction therapy in childhood ALL. In contrast to our hypothesis, the reason for the lack of significance was not due to more profound lymphopenia. The lack of ALC prognostic significance in our cohort could be protocol related or patient population (ethnicity) related. Further studies are needed in children with ALL with different ethnic backgrounds to validate the previous work regarding ALC significance before its incorporation in ALL prognostic models, especially in middle or low income countries. Disclosures: No relevant conflicts of interest to declare.

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