Early and late neurological complications after reduced-intensity conditioning allogeneic stem cell transplantation.
Neurological complications (NC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are common and life-threatening in most cases. They may involve either the central (CNS) or peripheral nervous system (PNS). The aim of this study was to describe incidence and characteristics of NC after reduced-intensity conditioning allo-HSCT (allo-RIC), an unexplored setting. For this purpose, we reviewed 191 consecutive patients who underwent this procedure at our institution between January 1999 and December 2006. The median follow-up for survivors was 48 months (3-98 months). RIC included fludarabine (Flu) 150 mg/m(2) in combination with busulfan (Bu) 8-10mg/kg (n=61), melphalan (Mel) 70-140 mg/m(2) (n=119), cyclophosphamide (Cy) 120 mg/kg (n=7), or low-dose total body irradiation (TBI) 2Gy (n=4). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A (CsA) in combination with methotrexate (MTX; n=134) or mycophenolate mofetil (MMF; n=52). Twenty-seven patients (14%) developed a total of 31 NC (23 CNS and 8 PNS) for a 4-year cumulative incidence of 16% (95% confidence interval [CI] 11-23). CNS complications included nonfocal encephalopathies in 11 patients, meningoencephalitis in 5 patients, and stroke or hemorrhage in 4. PNS complications consisted of 5 cases of mononeuropathies and 3 cases of polyneuropathies. Drug-related toxicity was responsible for 10 of the 31 events (32%) (8 caused by CsA). Interestingly, 14 of the 23 CNS events (61%) and only 1 of the 8 PNS complications (13%) appeared before day +100 (P=.01). Overall, patients presenting NC showed a trend for higher 1-year nonrelapse mortality (NRM) (37% versus 20%, P=.08). In patients with CNS involvement, 1-year NRM was significantly worse (42% versus 20%, P=.02). CNS NC also had a negative impact on 4-year overall survival (OS; 33% versus 45%, P=.05). In conclusion, our study showed that NC are observed after allo-RIC and have diverse features. NC affecting the CNS have earlier onset and worse outcome than those involving the PNS.
Barba
Pere
P
Hematology Department and Stem Cell Transplantation Program, Hospital de Santa Creu i Sant Pau, Autonomous University of Barcelona, Spain.
Piñana
Jose Luis
JL
Valcárcel
David
D
Querol
Luis
L
Martino
Rodrigo
R
Sureda
Anna
A
Briones
Javier
J
Delgado
Julio
J
Brunet
Salut
S
Sierra
Jorge
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000209:etiology; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D006402:Hematologic Diseases / Q000150:complications / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008590:Meningoencephalitis / Q000453:epidemiology / Q000209:etiology; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D009422:Nervous System Diseases / Q000453:epidemiology / Q000209:etiology*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D010523:Peripheral Nervous System Diseases / Q000453:epidemiology / Q000209:etiology; D011183:Postoperative Complications / Q000453:epidemiology* / Q000209:etiology; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D055815:Young Adult
D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine