Reduced intensity allogeneic umbilical cord blood transplantation in children and adolescent recipients with malignant and non-malignant diseases

The aim was to evaluate two transplant strategies for patients who lack HLA-identical donors, namely HLA-A, HLA-B or -DRb1 mismatched unrelated donor (MM URD) transplants (n ¼ 14) and umbilical cord blood transplants (UCB, n ¼ 27). Diagnosis, disease stage and age were similar in the two groups. Cell dose was lower in the UCB group (Po0.001). Median time to ANC of 40.5 Â 10 9 /l was 30 days in the UCB group and 17 days in the MM URD group (P ¼ 0.002). Engraftment of plt was delayed in the UCB group (P ¼ 0.03). The UCB patients required fewer erythrocyte transfusions (P ¼ 0.001). At 100 days, complete donor chimerism for CD3 was 63 and 44% in the UCB and MM URD groups, respectively. Acute GVHD of grades II-IV were 30% in the UCB group and 21% in the MM URD group. The corresponding figures for chronic GVHD were 9 and 20%, respectively. TRM was 30% in the UCB patients and 50% in the MM URD patients. Three-year survival was 66% in the UCB group and 14% in the MM URD group (P ¼ 0.006). Although the material is small and heterogeneous, engraftment was delayed, leukocyte chimerism was not significantly different and survival was superior using UCB rather than MM URD transplants.

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor

Ringdén

Okas

Uhlin

et al. 2008

“…Although it has been shown that a RIC regimen may lead to UCB engraftment in childhood leukemia, 24 some reports suggest that engraftment may be poor in patients with other diseases. [25][26][27] Only one previous patient with a solid tumor was reported to engraft successfully after RIC regimen and UCBT. 28 The objective of this pilot trial was therefore to examine engraftment after RIC of partially matched UCB in children with relapsed or refractory neuroblastoma.…”

Section: Introductionmentioning

confidence: 99%

Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial

Jubert

Wall

Grimley

et al. 2010

Relapsed or refractory neuroblastoma is uniformly fatal. We hypothesized that allogeneic response could provide a platform for immunotherapy in neuroblastoma. We therefore undertook a pilot trial of unrelated cord blood transplantation after reduced intensity conditioning regimen (RIC) in children with relapsed neuroblastoma to assess engraftment and tolerability in this heavily pretreated population. The RIC included CY (50 mg/kg, day À6), fludarabine (40 mg/m 2 , days À6 to À2), total body irradiation (200 cGy, day À1), and rabbit antithymocyte globulin (2.5 mg/kg, days À3 to À1). Six patients were enrolled: four were in partial responsive relapse, one with a mixed response and one in refractory relapse. All patients tolerated the regimen well and had donor engraftment with full neutrophil and plt recovery (median time 12 and 35 days, respectively). One patient never experienced neutropenia and another did not need plt transfusions. All patients progressed after transplant (median time 55 days, 26-180 days). Natural killer (NK) cell counts were normal within 2 months, whereas T-cell recovery was slower. In conclusion, unrelated cord blood engrafts after RIC in children with refractory neuroblastoma. Future research should be aimed at transplanting patients with minimal residual disease, using less intensive immunosuppression and adding NK-cell based post transplant immunotherapy.

“…These older patients make up a large population of patients with hematological malignancies who would potentially benefit from RIC UCB transplantation strategies, and this is reflected in the growing number of publications in the area. [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] Outcomes after RIC UCB transplantation have been encouraging, with most patients achieving prompt neutrophil recovery and donor chimerism plus promising PFS and OS (Table 3). There is variability in the incidence of acute (10-60%) and chronic (10-40%) GVHD, which may be related to differences in the conditioning regimen, post transplantation immunosuppression, and the number of UCB units composing the graft and ethnic heterogeneity of the study population.…”

Section: Ucb Reduced-intensity Conditioning Transplantationmentioning

confidence: 99%

Future of cord blood for oncology uses

Brunstein

Weisdorf

2009

The utilization of umbilical cord blood (UCB) as a source of stem cells for transplantation has grown substantially in the last decade. Already an established practice for the treatment of children with hematological malignancies, its application for the treatment of adults is also expanding. The development of the double UCB and reduced-intensity transplantation platforms have contributed to this expansion. Recent registry-based analysis and ongoing single institution and multicenter clinical trials are investigating ways to make UCB transplantation more widely available. We review here the background data on the utilization of UCB for the treatment of hematological malignancies, and discuss the current challenges and future directions in the field of UCB transplantation.