Outcomes of transplantation with matched-sibling and unrelateddonor bone marrow in children with leukaemia

169

119

Summary:Quantitative competitive PCR was used to monitor the quantity of cytomegalovirus (HCMV) in 1647 blood samples from 110 BMT recipients. DNAemia was detected in 49/110 (45%) of the patients, of whom 15/49 experienced HCMV disease. Peak virus load during surveillance was elevated in symptomatic (median 4.5 log 10 genomes/ml) vs asymptomatic patients (median 3.6 log 10 genomes/ml, P = 0.002) and was also significantly elevated in HCMV seropositive recipients of seronegative marrow, (R+D−, median 5.0 log 10 ), compared to those in the R−D− and R+D+ groups (P Ͻ 0.01 and Ͻ0.005). Odds ratios for disease per 0.25 log 10 increase in viral load, recipient seropositivity and aGVHD were 1.43 (P = 0.004), 6.60 (P = 0.05) and 3.17 (P = 0.08), respectively. In multivariate logistic regression analysis only elevated viral load remained a significant risk factor for HCMV disease. The computed disease probability viral load curve showed a rapid increase in disease risk at viral loads between 3.8 and 5.5 log 10 genomes/ml in blood, and odds ratios for disease were determined for different threshold viral loads. These data demonstrate the central role of viral load in the pathogenesis of HCMV in BMT recipients and provide an additional marker for targeting and monitoring therapy.

Section: Discussionsupporting

confidence: 83%

Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease

Gor

Sabin

Prentice

et al. 1998

169

119

“…Increasing the TBI dose led to decreased relapse rates, but this was offset by increased treatment-related mortality. 3 Alternatively, many investigators sought improved preparative regimen efficacy, by incorporating supplemental chemotherapy agents such as busulphan, 4 cytarabine, 5 or etoposide. [6][7][8] Previous clinical studies of one of these novel regimens, total body irradiation, etoposide and cyclophosphamide combined with allogeneic bone marrow transplantation for adults with acute leukemia have yielded mixed results.…”

mentioning

confidence: 99%

Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide

Duerst

Horan

Liesveld

et al. 2000

Summary:Marrow-ablative chemo-radiotherapy followed by hematopoietic stem cell rescue from an allogeneic source improves outcomes for children with high-risk acute leukemia. The first effective pre-transplant preparative regimens consisted of high-dose cyclophosphamide (CY) and total body irradiation (TBI). Subsequent attempts have been made to improve leukemia-free survival, by adding other chemotherapy agents to these agents. In previous clinical studies of total body irradiation, etoposide, cyclophosphamide (TBI-VP-16-Cy) in adult allogeneic bone marrow transplantation, there has been a high incidence of severe regimen-related toxicity. In this study, we investigated the safety and efficacy of this combination in 41 children who received TBI (12-14 Gy), VP-16 (30 mg/kg), and CY (60 mg/kg × 2) and then either matched sibling or alternative donor transplants for acute leukemia. There was only one case of fatal regimen-related toxicity. The estimated 3-year event-free survival for patients with early or intermediate stage disease was 68% (53-88%). The estimated event-free survival of patients with advanced disease was 17% (5-59%). TBI-VP16-CY is safe in pediatric transplantation, and it has good efficacy for transplant recipients with less advanced disease. outcomes for both adults and children by augmenting the anti-leukemic activity of this combination. Increasing the TBI dose led to decreased relapse rates, but this was offset by increased treatment-related mortality. 3 Alternatively, many investigators sought improved preparative regimen efficacy, by incorporating supplemental chemotherapy agents such as busulphan, 4 cytarabine, 5 or etoposide. [6][7][8] Previous clinical studies of one of these novel regimens, total body irradiation, etoposide and cyclophosphamide combined with allogeneic bone marrow transplantation for adults with acute leukemia have yielded mixed results. [6][7][8] To assess the safety and efficacy of this combination in pediatric patients, we evaluated the outcomes of 41 children and adolescents who received allogeneic bone marrow transplants for acute leukemia after total body irradiation, etoposide and cyclophosphamide. Patients and methods EligibilityThe pediatric bone marrow recipients included in this analysis were treated between September 1990 and October 1998 at the University of Rochester Medical Center. Patients were followed until 1 April 1999. During this time, all patients between the ages of 1 and 19 years who were receiving their first sibling or unrelated donor bone marrow transplant, and had acute lymphoblastic leukemia (FAB classification 1 or 2) or acute undifferentiated leukemia, were treated with this regimen. Patients with AML in undelayed first remission with matched sibling donors were treated on Pediatric Oncology Group protocols and not included in this analysis. All other pediatric patients who received allogeneic bone marrow transplants for AML were treated with this regimen. Two patients receiving second transplants received this preparative regimen; differen...

“…They used T-cell depletion for GVHD prophylaxis. 19 Our findings revealed that UD-BMT using FK-506 and MTX7mPSL for prophylaxis of GVHD is as safe and useful as BMT from HLA-identical family donors in children with hematological malignancy.…”

Section: Discussionmentioning

confidence: 63%

Unrelated donor bone marrow transplantation for 100 pediatric patients: a single institute's experience

Yumura‐Yagi

Inoue

Sakata

et al. 2005

Summary:In all, 100 unrelated donor bone marrow transplantations (UD-BMT) were performed in our institute between October 1993 and January 2003. Of 93 evaluable patients, 73 patients had hematological malignancy, 13 had nonmalignancy and seven had lymphoproliferative disease. The estimated 9-year event-free survival (EFS) rate was 57.175.5% in all patients. In the following analyses of the patients with hematological malignancy, the standard group had significantly better EFS than the high-risk group (61.577.0 vs 35.679.7%, P ¼ 0.02), and the EFS rate of the tacrolimus (FK-506) þ methotrexate (MTX)7methylprednisolone prophylactic group for graft-versus-host disease was superior to that of the FK-506 without MTX group (75.778.0 vs 55.877.6%, P ¼ 0.02). When we compared the EFS rates of the FK506 þ MTX7methylprednisolone (mPSL) group and the HLA-matched related donor BMT group in our institute, these were almost similar (75.778.1 vs 68.47 9.3%). Therefore, UD-BMT using FK-506 þ MTX7 mPSL is a safe and useful method for children with hematological malignancy who require allogeneic BMT.