Umbilical Cord Blood Transplantation Using Reduced-Intensity Conditioning without Antithymocyte Globulin in Adult Patients with Severe Aplastic Anemia

Abstract

A B S T R A C T Umbilical cord blood transplantation (UCBT) is a possible option for patients with aplastic anemia (AA) without a related or unrelated HLA-matched donor, particularly if immunosuppressive therapy (IST) has failed or transplantation is urgently needed. However, a higher rate of graft failure after UCBT remains a major problem, and the optimal conditioning regimen for stable engraftment after UCBT has not been established. Here we investigated 6 adult patients with AA who underwent UCBT using a reduced-intensity conditioning (RIC) regimen comprising fludarabine 125 mg/m 2 , cyclophosphamide 120 mg/kg, and 4 Gy of total body irradiation (Flu/CY/TBI4Gy) without antithymocyte globulin (ATG). Five patients underwent UCBT after IST failure, and 1 patient underwent UCBT as a first-line treatment due to a fulminant clinical finding of a neutrophil count of 0, despite granulocyte colony-stimulating factor administration. Regarding graft-versus-host disease (GVHD) prophylaxis, 2 patients received tacrolimus plus short-term methotrexate and 4 patients received tacrolimus plus mycophenolate mofetil, and all patients achieved sustained engraftment of both neutrophils and platelets, at a median of 17.5 days (range, 14 to 37 days) and 38.5 days (range, 31 to 86 days), respectively, with complete donor chimerism confirmed in all patients at a median of 14 days (range, 14 to 32 days). Three patients developed grade II acute GVHD (aGVHD), but grade III/IV aGVHD was not observed, whereas 4 patients developed chronic GVHD involving only skin. At the time of this report, all 6 patients were alive without the need for blood transfusion, at a median follow-up of 16 months (range, 12 to 131 months). Although further study is needed, our findings suggest that conditioning with Flu/CY/TBI4Gy without ATG might allow stable engraftment in UCBT for adults with AA.

A Patient with Kabuki Syndrome Mutation Presenting with Very Severe Aplastic Anemia

“…The Japanese guideline on hematopoietic stem cell transplantation (HSCT) for adult AA states that HSCT is recommended as a curative therapy for patients up to 59 years of age having fulminant AA. Further, in the absence of an HLA-identical sibling donor, alternative HSCT, including CBT, may be considered as a curative therapeutic option [11,12]. Our patient did not respond to G-CSF and had no neutrophils for 3 consecutive weeks, indications which were nearly compatible with those for fulminant AA.…”

“…Because of unavailability of human leukocyte antigen (HLA)-identical or HLA-haploidentical donor, CBT was considered, and written informed consent for the same was obtained. The patient received reduced-intensity conditioning regimen, comprising fludarabine 120 mg/m 2 (30 mg/m 2 on days −5 to −2), melphalan 80 mg/m 2 (40 mg/m 2 on days −4 and −3), and total body irradiation at a dose of 4 Gy (2 Gy on each day −1 and 0) [11,12]. Then, 4 weeks after admission, the 4/6 HLA allele-matched umbilical cord blood cells were transplanted.…”

Anemia aplásica: un nuevo reto farmacológico en la práctica clínica

“…49 Otra alternativa es un trasplante de sangre de cordón umbilical, opción posible para los pacientes con anemia aplásica (AA) sin un donante emparentado o no emparentado con HLA, especialmente en pacientes donde no se evidencia mejora o respuesta frente a la terapia inmunosupresora (IST) o en pacientes donde se deba realizar el trasplante con urgencia. 50 Finalmente, se considera la opción de un trasplante de donante compatible sin relación familiar; sin embargo, suele ser descartada rápidamente debido al alto riesgo de complicaciones que condicionan al paciente a una mortalidad temprana. 51…”

Strategies to enhance graft performance in cord blood transplantation

“…There were only three graft failures, and the 1-year survival rate was 89%. Recently, a Japanese retrospective study on the unrelated CBT with fludarabine (125 mg/m 2 ), cyclophosphamide (120 mg/kg), and low dose TBI (4 Gy) without ATG in adults with SAA was reported[41]. Although there were only six patients, all patients were engrafted and survived with a lower cell dose (median, 2.9 × 10 7 /kg; range, 2.2 to 4.6) than that used in the previous French study(median, 4.3 × 10 7 /kg in single CBT; median, 3.0 × 10 7 /kg in double CBT).…”