scholarly journals Late isolated central nervous system relapse in childhood B-cell acute lymphoblastic leukemia treated with intensified systemic therapy and delayed reduced-dose cranial radiation: A report from the Children’s Oncology Group study AALL02P2

2021 ◽  
Author(s):  
Caroline Hastings ◽  
Yichen Chen ◽  
Meenakshi Devidas ◽  
A. Ritchey ◽  
Naomi Winick ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Systemic Therapy ◽  
Treatment Plan ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Small Sample ◽  
Central Nervous System Relapse ◽  
Cranial Radiation ◽  
Number Of Patients

Background: Patients with late, occurring ≥18 months post-diagnosis, isolated central nervous relapse (iCNS-R) of B-acute lymphoblastic leukemia (ALL) have excellent outcomes with chemotherapy plus cranial radiotherapy, with 5-yr overall survival (OS) approaching 80% in POG 9412. Subsequent relapse and radiation-related morbidity remain the causes of treatment failure and long-term sequelae. COG AALL02P2 aimed to maintain outcomes in patients with late iCNS-R using intensified chemotherapy and a decrease in cranial irradiation from 1800 to 1200 cGy. Procedures: COG AALL02P2 enrolled 118 eligible patients with B-ALL and early iCNS-R who received intensified systemic therapy, triple intrathecal chemotherapy and 1200 cGy cranial irradiation delivered at 12 months, with maintenance chemotherapy continuing until104 weeks post-diagnosis. Results: The 3-yr event-free and overall survival (EFS) and OS were 64.3±4.5% and 79.6±3.8%, with 46.1% (18/39) of relapses including the CNS. Of the 112 patients who completed therapy, 78 received protocol-specified radiation. Study enrollment was closed after interim monitoring analysis showed inferior EFS compared to POG 9412. Patients with initial NCI standard risk classification fared better than high risk patients. Conclusions: COG AALL02P2 showed inferior EFS but similar OS compared to POG 9412. Limitations included a small sample size, more intensive prior therapies, and a significant number of patients (34/118, 29%) who did not receive protocol-directed radiation due to early relapse prior to 1 year or did not otherwise follow the treatment plan. New approaches are needed to improve outcome for these patients and determine the optimal timing and dose of cranial radiation in the treatment of iCNS-R.

Prognostic Impact of Bone Marrow B Lymphocyte Precursors (hematogones) Detection in 95 Acute Lymphoblastic Leukemia Cases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4791-4791 ◽  
Author(s):  
Sylvain P Chantepie ◽  
Audrey Emmanuelle Dugué ◽  
Patrice Chevallier ◽  
Aline Schmidt-Tanguy ◽  
Véronique Salaün ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Impact ◽  
Hematopoietic Stem ◽  
Time Points ◽  
Number Of Patients

Abstract Abstract 4791 Acute lymphoblastic leukemia (ALL) multiparameter flow cytometry (MFC) study of bone marrow aspiration after chemotherapy is crucial for determining minimal residual disease (MRD). Hematogones (HGs) have to be distinguishing from leukemic cells in B-cell subtypes and could be quantify during follow-up. To date, the incidence of Hgs in ALL and their prognostic significance have not been investigated. The aim of this multicenter study was to quantify Hgs after chemotherapy in ALL adult patients and to define its prognostic value. We retrospectively analyzed the incidence of HGs in 95 ALL patients, 71 with B-ALL (75%), 24 (25%) with T-ALL in first line treatment. The median age was 37 years [8–71], 20% had t(9;22) cytogenetic abnormality, and 70% had abnormal karyotype. 4/5-color MFC analysis MRD and HGs were performed at different time point (TP) after diagnosis: TP1 (post-induction, day 45 [41–61], n=78), TP2 (post-consolidation, day 111 [94–144] 25, n=42), TP3 (post-intensification/before hematopoietic stem cell transplantation (HSCT), day 179 [125–268], n=58), TP4 (n=11), TP5 (n=17), TP6 (n=9) after a median of 33, 91 and 167 days after HSCT, respectively. A total of 39 patients (41%) relapsed with a median of 26 months [7.7–47.9]. Forty seven patients (50%) received an HSCT in a complete (98%) or partial remission (2%). At TP1, TP2, TP3, TP4, TP5, TP6, the median HGs [range] were as followed: 0.00 [0.00–6.90]%, 0.30 [0.00–11.2]%, 0.98 [0.00–33.00]%, 0.52 [0.00;23.00]%, 5.50 [0.00;25.00]%, 4.60 [0.00;34.00]%, 5.90 [0.32;11.80]%, respectively. Figure 1 showed the percentage of patients with negative MRD (Figure 1A) and detectable HGs (figure 1B) during the follow up of ALL patients. There is a progressive increase of the percentage of patients with detectable HGs during the time of treatment and follow-up. Interestingly, there was no correlation between age and HGs level while in physiological situation the HGs rate decreases with increasing age. There was a negative correlation between positive MRD and detectable HGs at TP1 (p=0.022) but not at TP3 (p=0.88). In univariate analysis positive MRD at P1 and P3, age (/10), the presence of t(9;22) and absence of HGs at TP3 (figure 2) were bad prognostic factors for relapse free-survival (RFS) and overall survival (OS). The presence of HGs at other different time of evaluation was not associated with a significant decrease of relapse or death. However, patients who had a negative MRD at TP1 and detectable HGs in the bone marrow at TP3 exhibited a better RFS and OS (p=0.018 and p=0.065 respectively). Patients who had negative MRD at TP3 and had detectable HGs at TP3 had also a better RFS and OS (p=0.007 and p=0.011, respectively) compared to patients with negative MRD at TP3 and without HGs (figure 3). In patients who had a positive MRD at TP1, detectable HGs at TP3 identified a subgroup of patient with favorable OS compared to patient with positive MRD at TP1 and without detectable HGs (p=0.072). These results should be taken with cautious because of the decreasing number of patients evaluated at different time points. However, HGs analysis could represent a new area of investigation in search of new prognostic factors in the context of adult ALL. Figure 1. Percentage of patients with (A) negative MRD and (B) detectable HGs at different time points after starting of treatment. Figure 1. Percentage of patients with (A) negative MRD and (B) detectable HGs at different time points after starting of treatment. Figure 2. Overall survival according to HGs status at TP3. Figure 2. Overall survival according to HGs status at TP3. Figure 3. Overall survival in patients with negative MRD at TP3 according to HGs status. Figure 3. Overall survival in patients with negative MRD at TP3 according to HGs status. Disclosures: No relevant conflicts of interest to declare.

Subtle primary hypothyroidism in patients treated for acute lymphoblastic leukemia

1991 ◽  
Vol 124 (4) ◽  
pp. 375-380 ◽  
Author(s):  
Titania Pasqualini ◽  
June McCalla ◽  
Stacy Berg ◽  
David G Poplack ◽  
Susan R Rose ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Primary Hypothyroidism ◽  
Craniospinal Irradiation ◽  
Central Nervous System Relapse ◽  
The Mean ◽  
Serum Tsh

Abstract. We evaluated serum thyroid hormone and thyroid antibody levels, the serum TSH response to TRH, and the circadian pattern of serum TSH in 10 children and adolescents after radiation therapy for acute lymphoblastic leukemia. Four patients had received central nervous system preventive cranial irradiation and intrathecal chemotherapy, and the remaining 6 patients were treated with craniospinal irradiation for central nervous system relapse. Serum total T4 and T3 concentrations were within the normal range and thyroid antibodies were negative in all patients. Four patients who had received craniospinal irradiation had low free T4 levels. Prior to TRH administration, the overall mean serum TSH concentration was 5.4±1.3 mU/l, and the mean peak response to TRH was 33±6.5 mU/l. Both were significantly increased when compared to the levels observed in our control population (p<0.05 and <0.025, respectively). The overall mean nadir diurnal TSH was 3.6±0.8 mU/l, and the mean peak nocturnal TSH was 6.9±1.3 mU/l, both significantly elevated when compared to normal children (p<0.025). The mean nocturnal TSH surge, however, was not significantly different from normal. Four of 6 children treated with craniospinal irradiation, and one of four children treated with cranial irradiation had increased basal and peak serum TSH concentrations in response to TRH. One of the patients treated with cranial irradiation had an abnormal nocturnal TSH surge. We conclude that subtle primary hypothyroidism is relatively common in patients with acute lymphoblastic leukemia, particularly in those who have been treated with craniospinal irradiation.

The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia.

1985 ◽  
Vol 3 (6) ◽  
pp. 776-781 ◽  
Author(s):  
S L George ◽  
J J Ochs ◽  
A M Mauer ◽  
J V Simone
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Fold Increase ◽  
Cranial Irradiation ◽  
Preventive Therapy ◽  
Intrathecal Methotrexate ◽  
Central Nervous System Relapse ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Therapy Studies

We assessed the influence of an initial isolated meningeal relapse on treatment outcome in 839 children with acute lymphoblastic leukemia (ALL) who were admitted to St Jude Children's Research Hospital (Memphis) from mid-1967 through mid-1979. The patients were entered in a series of five clinical trials (Total Therapy Studies V through IX), each designed to test one or more modifications of treatment for ALL. Two groups were compared: 699 children who received CNS prophylaxis (2,400-rad craniospinal irradiation or 2,400-rad cranial irradiation plus intrathecal methotrexate) v 56 who did not. Our results, obtained with a time-dependent covariate model and a matching technique, indicate a 2 to 3.5-fold increase in the risk of hematologic relapse or death among patients who experienced an isolated CNS relapse compared with similar patients (matched for leukocyte count and length of complete remission) who remained free of CNS involvement. Of the 107 children with an initial isolated CNS relapse, 89 (83%) have died or have had a subsequent relapse. There was no detectable difference in the rate of hematologic relapse or death after a CNS relapse between patients who had received preventive therapy and those who had not. We conclude that CNS prophylaxis is important both for the prevention of initial CNS leukemia and for reducing the risk of hematologic relapse or death subsequent to a CNS relapse.

Outcomes of a Randomized Trial of Hyperfractionated Cranial Radiation Therapy for Treatment of High-Risk Acute Lymphoblastic Leukemia: Therapeutic Efficacy and Neurotoxicity

2004 ◽  
Vol 22 (13) ◽  
pp. 2701-2707 ◽  
Author(s):  
Deborah P. Waber ◽  
Lewis B. Silverman ◽  
Lori Catania ◽  
William Mautz ◽  
Montse Rue ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Visual Memory ◽  
Lymphoblastic Leukemia ◽  
Verbal Learning ◽  
Free Survival ◽  
Cranial Radiation ◽  
Neuropsychologic Testing

Purpose We evaluated 8-year survival and late neuropsychologic toxicity in children with acute lymphoblastic leukemia treated in a randomized clinical trial to test whether hyperfractionated (twice daily) cranial radiation therapy (CRT) can reduce incidence and severity of late toxicities associated with 18 Gy of CRT. Patients and Methods Between 1987 and 1995, 369 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for high-risk acute lymphoblastic leukemia were randomly assigned to conventionally fractionated CRT (CFX) or hyperfractionated CRT (HFX) to a total dose of 18 Gy. Neuropsychologic testing was completed for 125 of 287 children in continuous complete remission. Event-free and overall survival, as well as neuropsychologic function, were compared for the two arms of the protocol. Results Eight-year event-free survival (± SE) was 80% ± 3% for children randomly assigned to CFX and 72% ± 3% for HFX (P = .06). Overall survival was 85% ± 3% for CFX and 78% ± 3% for HFX (P = .06). CNS relapses occurred in 2.8% of patients receiving CFX and 2.7% receiving HFX (P = .99). Cognitive function for both groups was solidly in the average range, with no group differences in intelligence, academic achievement, visuospatial reasoning, or verbal learning. Children on the HFX arm exhibited a modest advantage for visual memory (P < .05). Conclusion HFX provides no benefit in terms of cognitive late effects and may compromise antileukemic efficacy. HFX should not be substituted for conventionally dosed CRT in children who require radiation therapy for treatment of acute lymphoblastic leukemia.

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