Central nervous system prophylaxis in haematological malignancies

Wellwood, Jeremy; Taylor, Kerry

doi:10.1046/j.1445-5994.2002.00214.x

Cited by 17 publications

(9 citation statements)

References 51 publications

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“…Strategies to prevent CNS relapse include prophylactic IT chemotherapy, RT, systemic therapy, or a combination of these treatments (1). The Children’s Cancer Group showed that intensive chemotherapy with IT methotrexate during induction, consolidation, and delayed intensification was equivalent to whole brain RT (18 Gy) in preventing CNS relapse in children with ALL (16).…”

Section: Discussionmentioning

confidence: 99%

“…Leukemia involving the central nervous system (CNS) has traditionally resulted in a very poor prognosis, with efforts focused on preventing CNS relapse rather than treatment once relapse has occurred (1, 2). Without CNS prophylaxis, CNS involvement occurs in <5% of patients with acute myeloid leukemia (2) compared with 25% to 50% in patients with lymphoid leukemias.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

Walker

Shihadeh

Kantarjian

et al. 2014

International Journal of Radiation Oncology*Biology*Physics

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Purpose To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. Methods and Materials A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. Results The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was delivered to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P = .02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated with worse CNS progression-free survival. Conclusions Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

Walker

Shihadeh

Kantarjian

et al. 2014

International Journal of Radiation Oncology*Biology*Physics

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“…Furthermore, systemic therapy is associated with wide-spread toxicities. High-dose cytarabine is associated with liver dysfunction, cerebellar dysfunction, mucositis, diarrhea, rash, and fever [23]. High-dose methotrexate is associated with renal dysfunction, transient hepatitis, mucositis, and (rarely) neurotoxicity [24].…”

Section: Chemotherapymentioning

confidence: 99%

Novel therapies for relapsed acute lymphoblastic leukemia

Fullmer

O’Brien

Kantarjian

et al. 2009

Curr Hematol Malig Rep

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The outcome of salvage therapy for relapsed acute lymphoblastic leukemia (ALL) remains poor. Salvage therapy mimics regimens with activity in newly diagnosed ALL. Novel strategies under investigation as monotherapy or in combination with chemotherapy improve the treatment of relapsed disease. For some ALL subsets, specific therapies are indicated. The addition of targeted therapy in Philadelphia chromosome–positive ALL has improved responses in relapsed patients without resistance to available tyrosine kinase inhibitors. Nelarabine demonstrates activity as monotherapy in T-cell ALL and is approved by the US Food and Drug Administration. Clofarabine, a second-generation purine analogue approved in pediatric leukemia, has shown activity in adult acute leukemias including ALL and acute myeloid leukemia. The role of pegaspargase in adult ALL requires further investigation. The benefit of matched related-donor allogeneic stem cell transplantation is significant for standard-risk ALL but not for high-risk ALL. Development of new drugs and agents tailored to subset-specific cytogenetic-molecular characteristics remains vital to success in treating adult ALL.

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“…1 Although the natural history of leukemia/lymphoma has been known to include CNS disease, 2,3 recent advances in therapy leading to overall improved hematologic malignancy outcomes have increased the rates of patients presenting with this therapeutic challenge, primarily from poor CNS penetrance of cytotoxic and targeted therapy agents. 4,5 Although leukemia and lymphoma involving the CNS is generally associated with poor prognosis, 4–6 a prior study demonstrated that whole brain or craniospinal irradiation (CSI) still conferred a 12-month CNS progression-free survival rate of 77% in patients affected with acute leukemia. 1 With the continued discovery of novel chemotherapeutic and targeted regimens and improved survival rates for patients with hematologic malignancies, there is an increased focus on optimizing treatment toxicity profiles and patient quality of life, along with local and systemic disease control.…”

Section: Introductionmentioning

confidence: 99%

Craniospinal irradiation prior to stem cell transplant for hematologic malignancies with CNS involvement: Effectiveness and toxicity after photon or proton treatment

Gunther

Rahman

Dong

et al. 2017

Practical Radiation Oncology

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Purpose/Objective(s) Craniospinal irradiation (CSI) improves local control of leukemia/lymphoma with central nervous system (CNS) involvement; however, for adult patients anticipating stem cell transplant (SCT), cumulative treatment toxicity is a major concern. We evaluated toxicities and outcomes for patients receiving proton or photon CSI before SCT. Methods and materials We identified 37 consecutive leukemia/lymphoma patients with CNS involvement who received CSI before SCT at our institution. Photon versus proton toxicities during CSI, transplant, and through 100 days posttransplant were compared using Fisher exact and Wilcoxon rank sum tests. Long-term neurotoxicity, disease response, and overall survival were analyzed. Results Thirty-seven patients (23 photon, 14 proton) underwent CSI for CNS involvement of acute lymphoblastic leukemia (49%), acute myeloblastic leukemia (22%), chronic lymphocytic leukemia (3%), chronic myelocytic leukemia (14%), lymphoma (11%), and myeloma (3%). CSI was used for consolidation (30 patients, 81%) and gross disease treatment (7 patients, 19%). Median radiation dose (interquartile range) was 24 Gy (23.4–24) for photons and 21.8 Gy (21.3–23.6) for protons (P = .03). Proton CSI was associated with lower rates of Radiation Therapy Oncology Group grade 1–3 mucositis during CSI (7% vs 44%, P = .03): 1 grade 3 with protons versus 5 grade 1, 3 grade 2, and 2 grade 3 with photons. During CSI, other toxicities (infection, gastrointestinal symptoms) did not differ. Allogeneic stem cell transplant (SCT) was used in 95% of patients, with 53% of patients in remission before SCT. Myeloablative conditioning was used for 76%. During SCT admission and 100 days post-SCT, toxicities did not differ by CSI technique. Successful engraftment occurred in 95% of patients (P = .67). Progression or death occurred for 47% of patients, with only 1 CNS relapse. Conclusion In our cohort, CSI offered excellent local control for CNS-involved hematologic malignancies in the pre-SCT setting. Acute mucositis occurred less frequently with proton CSI with comparable peritransplant/long-term toxicity profile, suggesting the need to further explore the benefit/toxicity profile of this technique.

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Central nervous system prophylaxis in haematological malignancies

Cited by 17 publications

References 51 publications

Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

Novel therapies for relapsed acute lymphoblastic leukemia

Craniospinal irradiation prior to stem cell transplant for hematologic malignancies with CNS involvement: Effectiveness and toxicity after photon or proton treatment

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