Neurobehavioral toxicity of total body irradiation: a follow-up in long-term survivors

Peper, Martin; Steinvorth, Sarah; Schraube, P.; Früehauf, Stefan; Haas, Rainer; Kimmig, B.; Lohr, Frank; Wenz, Frederik; Wannenmacher, M.

doi:10.1016/s0360-3016(99)00442-3

Cited by 57 publications

(48 citation statements)

References 42 publications

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“…[7][8][9][10][11] Research that has assessed patients 6 months or longer post-HCT indicates some recovery of cognitive function after acute deficits. [7][8][9][11][12][13][14][15] However, to our knowledge, no prospective studies have followed HCT patients beyond 2 years after transplantation.…”

Section: Introductionmentioning

confidence: 99%

Prospective Neurocognitive Function Over 5 Years After Allogeneic Hematopoietic Cell Transplantation for Cancer Survivors Compared With Matched Controls at 5 Years

Syrjala

Artherholt

Kurland

et al. 2011

JCO

121

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A B S T R A C T PurposeResearch has documented cognitive deficits both before and after high-dose treatment followed by allogeneic hematopoietic cell transplantation (HCT), with partial recovery by 1 year. This study prospectively examined the trajectory and extent of long-term cognitive dysfunction, with a focus on 1 to 5 years after treatment. Patients and MethodsAllogeneic HCT recipients completed standardized neuropsychological tests including information processing speed (Trail Making A and Digit Symbol Substitution Test), verbal memory (Hopkins Verbal Learning Test-Revised), executive function (Controlled Oral Word Association Test and Trail Making B), and motor dexterity and speed (Grooved Pegboard). Survivors (n ϭ 92) were retested after 80 days and 1 and 5 years after transplantation. Case-matched controls (n ϭ 66) received testing at the 5-year time point. A Global Deficit Score (GDS) summarized overall impairment. Response profiles were analyzed using linear mixed effects models. ResultsSurvivors recovered significant cognitive function from post-transplantation (80 days) to 5 years in all tests (P Ͻ .0001) except verbal recall (P Ͼ .06). Between 1 and 5 years, verbal fluency improved (P ϭ .0002), as did executive function (P Ͻ .01), but motor dexterity did not (P Ͼ .15), remaining below controls (P Ͻ .0001) and more than 0.5 standard deviation below population norms. In GDS, 41.5% of survivors and 19.7% of controls had mild or greater deficits (NcNemar test ϭ 7.04, P ϭ .007). ConclusionAlthough neurocognitive function improved from 1 to 5 years after HCT, deficits remained for more than 40% of survivors. Risk factors, mechanisms and rehabilitation strategies need to be identified for these residual deficits.

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Section: Introductionmentioning

confidence: 99%

Prospective Neurocognitive Function Over 5 Years After Allogeneic Hematopoietic Cell Transplantation for Cancer Survivors Compared With Matched Controls at 5 Years

Syrjala

Artherholt

Kurland

et al. 2011

JCO

121

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“…Memory, attention, and information-processing deficits have been documented. [1][2][3][4][5][6] Some recovery of cognitive function after transplantation has been suggested by studies that assessed patients 6 months or longer following HCT. 3,5,7 In parallel with neuropsychologic test results, numerous imaging studies have determined that neurologic changes such as cortical atrophy and ventricular enlargement occur in some patients after HCT conditioning chemotherapy or total body irradiation and that cyclosporine or tacrolimus treatments for graft-versus-host disease (GVHD) after HCT have neurotoxicities.…”

Section: Introductionmentioning

confidence: 99%

Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant

Syrjala

Dikmen

Langer

et al. 2004

Blood

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Research indicates that myeloablative hematopoietic cell transplantation (HCT) impairs neurocognitive function. However, prospective studies on long-term effects are lacking. This longitudinal study examined neurocognitive changes over the first year in 142 adult recipients of allogeneic HC transplants who received neuropsychologic testing before transplantation and again after 80 days and 1 year. Age-, sex-, and education-adjusted population-based standardized scores were used for normative comparisons. Performance on all tests declined from before transplantation to 80 days (P < .05) and improved by 1 year (P < .05), returning to pretransplantation levels on all tests except for grip strength and motor dexterity. Although verbal fluency and memory recovered by 1 year, both were below norms at all 3 testing times (P < .01). Logistic regressions indicated that patients without chemotherapy, other than hydroxyurea, previous to HCT and patients not receiving chronic graft-versus-host disease (GVHD) medication at 1 year had lower risk of impaired function (P < .05). In conclusion, HCT was associated with significant generalized decline in neurocognitive performance at 80 days, with subsequent recovery to pretransplantation levels by 1 year for most survivors, except on motor tasks. Results indicate that long-term cognitive decrements, as distinct from motor disabilities, infrequently derive directly from HCT. (Blood.

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“…14 Another factor that can plausibly explain (at least part of) the initial rapid decline of brain volume may be the neurotoxicity of the aggressive conditioning regimen used here. 15,16 Brain tissue, already injured by repeated and persistent inflammatory insults, may have indeed been further damaged by the neurotoxicity of both chemotherapy and irradiation. This hypothesis is strengthened by the results of another recent AHSCT study of patients with MS, where a short-term dramatic increase in brain atrophy was suggested to be secondary to the neurotoxic effects of the agents used for immunoablation.…”

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confidence: 99%

A Three-Year Study of Brain Atrophy after Autologous Hematopoietic Stem Cell Transplantation in Rapidly Evolving Secondary Progressive Multiple Sclerosis

Rocca¹,

Mondria²,

Valsasina³

et al. 2007

American Journal of Neuroradiology

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Neurobehavioral toxicity of total body irradiation: a follow-up in long-term survivors

Cited by 57 publications

References 42 publications

Prospective Neurocognitive Function Over 5 Years After Allogeneic Hematopoietic Cell Transplantation for Cancer Survivors Compared With Matched Controls at 5 Years

Prospective Neurocognitive Function Over 5 Years After Allogeneic Hematopoietic Cell Transplantation for Cancer Survivors Compared With Matched Controls at 5 Years

Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant

A Three-Year Study of Brain Atrophy after Autologous Hematopoietic Stem Cell Transplantation in Rapidly Evolving Secondary Progressive Multiple Sclerosis

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