scholarly journals The risks of central nervous system relapse and leukoencephalopathy in patients receiving marrow transplants for acute leukemia

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 195-199 ◽  
Author(s):  
CB Thompson ◽  
JE Sanders ◽  
N Flournoy ◽  
CD Buckner ◽  
ED Thomas
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Leukemia ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Involvement ◽  
Intrathecal Methotrexate ◽  
Central Nervous System Relapse ◽  
Cns Relapse ◽  
Increased Risk

The records of 415 patients who received allogeneic marrow transplants for acute leukemia were reviewed to assess the risk of central nervous system (CNS) relapse and leukoencephalopathy after marrow transplantation. The Kaplan-Meier estimates of the probability of CNS relapse posttransplant were 13% for patients with acute lymphoblastic leukemia (ALL) and 2% for patients with acute nonlymphoblastic leukemia (ANL). Previous CNS disease was significantly correlated with an increased risk of CNS relapse in patients transplanted for ALL but not for ANL. In contrast, bone marrow involvement with leukemia at the time of transplant was associated with an increased risk of CNS relapse in patients with ANL but not in patients with ALL. Seventy-one patients with ALL did not receive posttransplant intrathecal methotrexate (IT- MTX) and 127 did. The probability of CNS relapse in these two groups was 38% and 7%, respectively (P less than .02). This protective benefit from IT-MTX was present in patients both with and without a history of CNS involvement or marrow involvement at the time of transplant. In patients with ANL, 116 patients did not receive posttransplant IT-MTX and 101 patients did, but no protection from CNS relapse was observed from IT-MTX irrespective of a patient's previous CNS history or marrow status at the time of transplant. Leukoencephalopathy was seen exclusively in patients who had received radiation and/or intrathecal chemotherapy to the CNS before preparation for marrow transplantation and posttransplant IT-MTX. In such patients the risk of leukoencephalopathy was 7%. From our data, it appears that posttransplant IT-MTX is a significant benefit for ALL patients in preventing CNS relapse after marrow transplantation. A similar benefit from posttransplant IT-MTX for ANL patients cannot be established from this study. In both groups, increasing total CNS therapy was associated with an increasing risk of leukoencephalopathy.

scholarly journals The risks of central nervous system relapse and leukoencephalopathy in patients receiving marrow transplants for acute leukemia

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 195-199 ◽  
Author(s):  
CB Thompson ◽  
JE Sanders ◽  
N Flournoy ◽  
CD Buckner ◽  
ED Thomas
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Leukemia ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Involvement ◽  
Intrathecal Methotrexate ◽  
Central Nervous System Relapse ◽  
Cns Relapse ◽  
Increased Risk

Abstract The records of 415 patients who received allogeneic marrow transplants for acute leukemia were reviewed to assess the risk of central nervous system (CNS) relapse and leukoencephalopathy after marrow transplantation. The Kaplan-Meier estimates of the probability of CNS relapse posttransplant were 13% for patients with acute lymphoblastic leukemia (ALL) and 2% for patients with acute nonlymphoblastic leukemia (ANL). Previous CNS disease was significantly correlated with an increased risk of CNS relapse in patients transplanted for ALL but not for ANL. In contrast, bone marrow involvement with leukemia at the time of transplant was associated with an increased risk of CNS relapse in patients with ANL but not in patients with ALL. Seventy-one patients with ALL did not receive posttransplant intrathecal methotrexate (IT- MTX) and 127 did. The probability of CNS relapse in these two groups was 38% and 7%, respectively (P less than .02). This protective benefit from IT-MTX was present in patients both with and without a history of CNS involvement or marrow involvement at the time of transplant. In patients with ANL, 116 patients did not receive posttransplant IT-MTX and 101 patients did, but no protection from CNS relapse was observed from IT-MTX irrespective of a patient's previous CNS history or marrow status at the time of transplant. Leukoencephalopathy was seen exclusively in patients who had received radiation and/or intrathecal chemotherapy to the CNS before preparation for marrow transplantation and posttransplant IT-MTX. In such patients the risk of leukoencephalopathy was 7%. From our data, it appears that posttransplant IT-MTX is a significant benefit for ALL patients in preventing CNS relapse after marrow transplantation. A similar benefit from posttransplant IT-MTX for ANL patients cannot be established from this study. In both groups, increasing total CNS therapy was associated with an increasing risk of leukoencephalopathy.

scholarly journals Concurrent hypopituitarism and leukemic retinopathy in a child with B-precursor acute lymphoblastic leukemia and isolated central nervous system relapse

2016 ◽  
Vol 23 (4) ◽  
pp. 431
Author(s):  
K.H. Wu ◽  
H.P. Wu ◽  
H.J. Lin ◽  
C.H. Wang ◽  
H.Y. Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Systemic Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Therapy ◽  
Central Nervous System Relapse ◽  
Cns Involvement ◽  
Lower Extremity Weakness ◽  
Cns Relapse

Hypopituitarism in leukemia is very rare. In addition, central nervous system (cns) relapse and leukemic retinopathy in childhood acute lymphoblastic leukemia (all) have declined with the use of modern systemic chemotherapy that includes cns prophylaxis. Here, we report the case of a 4-year-old girl who received chemotherapy and intrathecal therapy without cns radiation after a diagnosis of B-precursor all without cns involvement. Three months after chemotherapy completion, she presented with lower-extremity weakness and was diagnosed with an isolated cns relapse. Concurrent hypopituitarism and leukemic retinopathy were also found. After receiving craniospinal radiotherapy and systemic chemotherapy, her retinopathy and vision improved. She is now in complete remission, and she is still on chemotherapy according to the guideline from the Pediatric Oncology Group. Although rare, hypopituitarism and leukemic retinopathy should be taken into consideration in patients with cns involvement by leukemia.

scholarly journals Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 241-250
Author(s):  
FS Muriel ◽  
E Svarch ◽  
S Pavlovsky ◽  
M Eppinger-Helft ◽  
J Braier ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Intrathecal Methotrexate ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Cns Relapse ◽  
Wbc Count

In acute lymphoblastic leukemia (ALL), central nervous system (CNS) prophylaxis with cranial irradiation plus 5 doses of intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity started to be recognized as CT scan abnormalities and neuropsychologic alterations, mainly in children. Two questions were analyzed in the present report: (1) Will further doses of i.t. methotrexate and dexamethasone (i.t. MTX- DMT) decrease the incidence of CNS relapse in patients treated early in remission with cranium irradiation plus i.t. MTX-DMT even more? (2) Is i.t. MTX-DMT given during induction and maintenance equally as effective as cranium irradiation plus i.t. MTX-DMT? A randomized study was designed to answer the first question. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count less than 50,000 was 11% (15 of 135 patients) and was 11% (17 of 150) in the untreated group. In patients with a WBC count greater than 50,000, it was 16% (6/37) in the treated group and 19% (6/31) in the control group. No difference was observed according to treatment in both prognostic groups. Patients in this study were retrospectively compared with a consecutive protocol in which patients received 3 doses of i.t. MTX-DMT alone during induction plus 3 doses weekly during the first month of remission and every 3 mo thereafter. The incidence of primary CNS leukemia at 60 mo in patients with a WBC count less than 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. This difference was not significant. However, the relapse-free survival at 60 mo was 26% and 41%, respectively, (p less than 0.0005). The incidence of primary CNS relapse in patients with a WBC count more than 50,000 at 48 mo was 28% in the irradiated group and 42% in the nonirradiated group. The difference was not significant. The duration of complete remission was similar, remaining at 15% and 16% of patients disease-free at 48 mo, respectively. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) the use of i.t. MTX-DMT alone compares similarly with cranial irradiation plus i.t. MTX-DMT in the incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count less than 50,000 were significantly longer in those without cranial irradiation.

scholarly journals Isolated central nervous system leukemiarelapse presenting as Guillain-Barré-like syndrome: A case report

2020 ◽  
Vol 8 (3) ◽  
pp. 51-53
Author(s):  
Marwa Abd El-Maksoud ◽  
yasmine El Chazli ◽  
Yasser Wali
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphoblastic Leukemia ◽  
Lower Limbs ◽  
Central Nervous System Relapse ◽  
Fluid Analysis ◽  
Cns Relapse ◽  
Electrophysiological Studies ◽  
Blast Cells ◽  
Guillain Barré

We report the clinical picture, management and outcome of a 14-year-old boy treated for acute lymphoblastic leukemia (ALL) in whom isolated central nervous system relapse manifested by a Guillain-Barré-like syndrome (GBS). While on maintenance chemotherapy for his first CNS-relapse, he developed acute progressive lower motor neuron right facial palsy and marked hypotonia and areflexia of both lower limbs with otherwise no systemic manifestations. Vincristine-induced neuropathy (VIN) was suspected but his electrophysiological evaluation revealed a proximal demyelinating polyradiculoneuropathy pattern suggestive of GBS, but his cerebrospinal fluid analysis showed increased protein and infiltration by 95% leukemic blast cells. Immunoglobulins and chemotherapy were initiated. Although GBS in children with ALL is very rare, differentiating it from VIN by electrophysiological studies and excluding CNS relapse is crucial to determine the proper treatment and ensure a better clinical outcome.

scholarly journals Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia

Blood ◽  
2012 ◽  
Vol 119 (7) ◽  
pp. 1658-1664 ◽  
Author(s):  
Jitesh D. Kawedia ◽  
Chengcheng Liu ◽  
Deqing Pei ◽  
Cheng Cheng ◽  
Christian A. Fernandez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Multivariate Analyses ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Relapse ◽  
Relapse Risk ◽  
Increased Risk ◽  
The Impact ◽  
Risk Of Relapse

Abstract We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti–asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10−8) in patients whose sera was positive (17.7 ± 18.6 L/h per m2) versus nega-tive (10.6 ± 5.99 L/h per m2) for anti–asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti–asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti–asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse.

Central nervous system morbidity following an initial isolated central nervous system relapse and its subsequent therapy in childhood acute lymphoblastic leukemia.

1985 ◽  
Vol 3 (5) ◽  
pp. 622-626 ◽  
Author(s):  
J J Ochs ◽  
G Rivera ◽  
R J Aur ◽  
H O Hustu ◽  
R Berg ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cns Infection ◽  
Central Nervous System Relapse ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Cranial Nerve Palsies ◽  
Cns Toxicity

The frequency and types of major CNS toxicity and morbidity were analyzed in 107 children with acute lymphoblastic leukemia (ALL) following an isolated primary CNS relapse. Seventy-nine (73%) have had multiple subsequent marrow or CNS relapses requiring intensive and prolonged therapy to the CNS. Median survival time is two years. Of these 79 patients, two thirds have had one or more types of major CNS toxicity, including epileptiform seizures (35), moderate to severe structural abnormalities (24 of 27 evaluated), major motor disabilities (9), blindness (2), CNS infection (6), cranial nerve palsies (2), and intracranial lymphoma (2). The remaining 28 patients (26%) have had no or one additional CNS relapse and have received therapy for a median of eight years. One half of this surviving group of patients have had major CNS toxicity, including seizures (9), major motor disability (2), and intracranial calcifications (12/19). When neuropsychologic evaluations were compared between the 28 survivors and 50 of their contemporaries who had been in initial continuous complete remission, the CNS survivors had significantly lower Full Scale IQ scores (83 +/- 16 v 99 +/- 14, P = less than .001) with similarly lower measures of academic performance. The relative contributions of meningeal leukemia itself and intrathecal or radiation therapy to these effects cannot be determined. Since major CNS sequelae occurred in the majority of patients who had a primary isolated CNS relapse, and the frequency of CNS relapse is dependent on the efficacy of the method of CNS prophylaxis, the best method of avoiding major CNS sequelae is the most effective form of CNS prophylaxis.

Treatment of acute lymphoblastic leukemia in adults: results of the L-10 and L-10M protocols.

1983 ◽  
Vol 1 (8) ◽  
pp. 462-470 ◽  
Author(s):  
P Schauer ◽  
Z A Arlin ◽  
R Mertelsmann ◽  
C Cirrincione ◽  
A Friedman ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Methotrexate ◽  
Central Nervous System Relapse ◽  
Maintenance Program ◽  
Consolidation Phase

Two successive protocols (L-10 and L-10M) employing multidrug induction therapy with vincristine, prednisone, and doxorubicin (Adriamycin) plus an intensive consolidation phase and maintenance program have led to a significant improvement in the prognosis of adult acute lymphoblastic leukemia (ALL). The complete remission (CR) rates for the 34 patients entered on the L-10 protocol and the 38 patients entered on the L-10M protocol were 85% and 84%, respectively. The median duration of remission has not yet been reached for either the L-10 (median follow-up, 5.5 years; range, 3.5-7.5 years) or the L-10M protocol (median follow-up, 2.5 years; range, 1-3.5 years). The median survival time has not yet been reached for the L-10M protocol. Central nervous system prophylaxis with intrathecal methotrexate alone was effective in preventing central nervous system relapse. An analysis of possible prognostic factors indicated that patients less than 25 years of age had a higher CR rate than older patients (p = 0.02). Patients with an initial leukocyte count below 15,000/microL experienced longer remissions than patients with a leukocyte count above 15,000/microL (p = 0.008), and patients who achieved CR within the first month of therapy were in remission longer than those requiring a longer time to achieve CR (p = 0.04). Patients with T cell ALL did not have a poorer prognosis than other patients treated on these protocols. The L-10 and L-10M protocols were well tolerated with minimal morbidity.

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