Unrelated donor bone marrow transplantation for children with acute leukemia.

1997 ◽  
Vol 15 (2) ◽  
pp. 557-565 ◽  
Author(s):  
S M Davies ◽  
J E Wagner ◽  
X O Shu ◽  
B R Blazar ◽  
E Katsanis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Acute Leukemia ◽  
Marrow Transplantation ◽  
Chronic Gvhd ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Acute Leukemias ◽  
Donor Bone Marrow

PURPOSE To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias. PATIENTS AND METHODS Between June 1985 and December 1994, 50 children with acute leukemia (15 acute myelogenous leukemia [AML], 35 acute lymphoblastic leukemia [ALL]; 22 greater than second complete remission [CR]) received BMT from a URD at the University of Minnesota. Ages ranged from 0.9 to 17.5 years (median, 8.8). Median follow-up is 2.1 years (range, 1 to 7.3). Thirty patients (60%) received bone marrow fully matched at HLA-A,B and DRB1; 20 (40%) received bone marrow with a major or minor mismatch at a single HLA-A or B locus. RESULTS The median time to neutrophil engraftment was day 24 (range, 14 to 42 days) in those receiving matched and day 25 (range, 15 to 32 days) in those receiving mismatched marrow (P = .35). The incidence of grades III to IV graft-versus-host disease (GVHD) was 23% (95% confidence interval [CI], 7% to 39%) in matched and 32% (95% CI, 8% to 52%) in HLA-mismatched patients (P = .57). The incidence of chronic GVHD was 50% (95% CI, 28% to 72%) in matched and 57% (95% CI, 23% to 91%) in mismatched patients (P = .80). Disease-free survival for patients with ALL is 37% (95% CI, 21% to 53%) at 1 year and 30% (95% CI, 15% to 46%) at 2 years; for patients with AML, 53% (95% CI, 28% to 78%) at 1 year and 33% (95% CI, 6% to 60%) at 2 years. CONCLUSION URD BMT is an effective treatment for children with poor-prognosis acute leukemia and should be considered for all high-risk patients. Early referral of patients is strongly recommended.

scholarly journals Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 270-276 ◽  
Author(s):  
AH Filipovich ◽  
RS Shapiro ◽  
NK Ramsay ◽  
T Kim ◽  
B Blazar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Chronic Gvhd ◽  
Severe Combined Immunodeficiency ◽  
Suppressive Therapy ◽  
Unrelated Donor ◽  
Actuarial Survival ◽  
Donor Bone Marrow ◽  
Chediak Higashi Syndrome

Unrelated donor marrow transplantation was undertaken in eight infants with severe combined immunodeficiency (SCID) and two children each with Wiskott-Aldrich syndrome (WAS) and Chediak-Higashi syndrome (CHS) who did not have histocompatible siblings. Donors for three patients were phenotypically matched at all HLA-A, B, Dr, and Dw loci, whereas nine donors were mismatched from the recipients at one of the HLA-A or B loci but phenotypically identical at evaluable D loci. All but one patient received conditioning chemotherapy and/or radiotherapy before infusion of donor marrow, which was not T-cell depleted. Prophylaxis for graft-versus-host disease (GVHD) consisted of methotrexate and prednisone combined with either cyclosporine A (six patients), antithymocyte globulin (five patients), or anti-CD5 ricin A chain immunotoxin (one patient). All patients engrafted with donor cells, and only 4 of 12 experienced any GVHD (1 of 8 SCID, 1 of 2 WAS, 2 of 2 CHS). Two children who developed grade II and two who developed grade III GVHD were successfully treated and all are now alive, off immuno- suppressive therapy, with no evidence of chronic GVHD greater than 18 months after transplant. Ten patients are alive with excellent immunoreconstitution greater than or equal to 1 year to greater than or equal to 3 years after transplant; actuarial survival is predicted to be 83% with a median follow-up of 2 years. Two children with SCID succumbed to pre-existing opportunistic infection early posttransplant. We conclude that closely matched unrelated donor bone marrow transplantation can correct congenital immunodeficiencies including variants of SCID, WAS, and CHS, with an acceptably low incidence of transplant-related complications, principally GVHD.

scholarly journals Unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 877-881
Author(s):  
P McGlave ◽  
E Scott ◽  
N Ramsay ◽  
D Arthur ◽  
B Blazar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Chronic Gvhd ◽  
Myelogenous Leukemia ◽  
Stable Phase ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Normal Peripheral Blood

Eight patients received allogeneic bone marrow transplantation (BMT) as therapy for chronic myelogenous leukemia (CML) using marrow from unrelated donors. In all cases donors and recipients were HLA DR identical and had low MLC reactivity. In three cases recipients received marrow that was identical at the HLA A,B loci. In five cases HLA identity differed for one HLA A locus antigen. The unrelated donor search interval ranged from 2 to 28 months (median, 3 months). All recipients were prepared with a combination of cyclophosphamide, 60 mg/kg/d administered intravenously (IV) (days -6,-5) and with total body irradiation administered in 165 cGy fractions twice daily for four days (days -4, -3, -2, -1). Engraftment occurred in all cases (range, 18 to 48 days; median, 35 days), and return to a complete Philadelphia chromosome (Ph′) negative state was documented in six of eight cases. Moderate or severe acute graft v host disease (GVHD) occurred in seven of eight cases, and extensive chronic GVHD in four of six evaluable recipients. A B cell lymphoproliferative disorder developed in one patient. Four recipients have died within 2 to 4 months of transplant. Four of eight patients survive at 11+ to 24+ months following transplantation (median, 15+ months) with normal peripheral blood counts and without evidence of leukemia. Current Karnofsky activity assessments are 90% or 100% in all survivors. Curative therapy of CML has been available only to the minority of patients eligible for sibling donor BMT. Unrelated donor BMT can be effective in the treatment of CML and may be particularly useful in this disorder since the prolonged stable phase of disease offers an opportunity to locate suitable donors.

scholarly journals Unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 877-881 ◽  
Author(s):  
P McGlave ◽  
E Scott ◽  
N Ramsay ◽  
D Arthur ◽  
B Blazar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Chronic Gvhd ◽  
Myelogenous Leukemia ◽  
Stable Phase ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Normal Peripheral Blood

Abstract Eight patients received allogeneic bone marrow transplantation (BMT) as therapy for chronic myelogenous leukemia (CML) using marrow from unrelated donors. In all cases donors and recipients were HLA DR identical and had low MLC reactivity. In three cases recipients received marrow that was identical at the HLA A,B loci. In five cases HLA identity differed for one HLA A locus antigen. The unrelated donor search interval ranged from 2 to 28 months (median, 3 months). All recipients were prepared with a combination of cyclophosphamide, 60 mg/kg/d administered intravenously (IV) (days -6,-5) and with total body irradiation administered in 165 cGy fractions twice daily for four days (days -4, -3, -2, -1). Engraftment occurred in all cases (range, 18 to 48 days; median, 35 days), and return to a complete Philadelphia chromosome (Ph′) negative state was documented in six of eight cases. Moderate or severe acute graft v host disease (GVHD) occurred in seven of eight cases, and extensive chronic GVHD in four of six evaluable recipients. A B cell lymphoproliferative disorder developed in one patient. Four recipients have died within 2 to 4 months of transplant. Four of eight patients survive at 11+ to 24+ months following transplantation (median, 15+ months) with normal peripheral blood counts and without evidence of leukemia. Current Karnofsky activity assessments are 90% or 100% in all survivors. Curative therapy of CML has been available only to the minority of patients eligible for sibling donor BMT. Unrelated donor BMT can be effective in the treatment of CML and may be particularly useful in this disorder since the prolonged stable phase of disease offers an opportunity to locate suitable donors.

scholarly journals High-risk HLA alleles for severe acute graft- versus -host disease and mortality in unrelated donor bone marrow transplantation

Haematologica ◽  
2016 ◽  
Vol 101 (4) ◽  
pp. 491-498 ◽  
Author(s):  
Satoko Morishima ◽  
Koichi Kashiwase ◽  
Keitaro Matsuo ◽  
Fumihiro Azuma ◽  
Toshio Yabe ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Unrelated Donor ◽  
Hla Alleles ◽  
Graft Versus Host ◽  
Donor Bone Marrow ◽  
Acute Graft

scholarly journals Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 270-276 ◽  
Author(s):  
AH Filipovich ◽  
RS Shapiro ◽  
NK Ramsay ◽  
T Kim ◽  
B Blazar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Chronic Gvhd ◽  
Severe Combined Immunodeficiency ◽  
Suppressive Therapy ◽  
Unrelated Donor ◽  
Actuarial Survival ◽  
Donor Bone Marrow ◽  
Chediak Higashi Syndrome

Abstract Unrelated donor marrow transplantation was undertaken in eight infants with severe combined immunodeficiency (SCID) and two children each with Wiskott-Aldrich syndrome (WAS) and Chediak-Higashi syndrome (CHS) who did not have histocompatible siblings. Donors for three patients were phenotypically matched at all HLA-A, B, Dr, and Dw loci, whereas nine donors were mismatched from the recipients at one of the HLA-A or B loci but phenotypically identical at evaluable D loci. All but one patient received conditioning chemotherapy and/or radiotherapy before infusion of donor marrow, which was not T-cell depleted. Prophylaxis for graft-versus-host disease (GVHD) consisted of methotrexate and prednisone combined with either cyclosporine A (six patients), antithymocyte globulin (five patients), or anti-CD5 ricin A chain immunotoxin (one patient). All patients engrafted with donor cells, and only 4 of 12 experienced any GVHD (1 of 8 SCID, 1 of 2 WAS, 2 of 2 CHS). Two children who developed grade II and two who developed grade III GVHD were successfully treated and all are now alive, off immuno- suppressive therapy, with no evidence of chronic GVHD greater than 18 months after transplant. Ten patients are alive with excellent immunoreconstitution greater than or equal to 1 year to greater than or equal to 3 years after transplant; actuarial survival is predicted to be 83% with a median follow-up of 2 years. Two children with SCID succumbed to pre-existing opportunistic infection early posttransplant. We conclude that closely matched unrelated donor bone marrow transplantation can correct congenital immunodeficiencies including variants of SCID, WAS, and CHS, with an acceptably low incidence of transplant-related complications, principally GVHD.

scholarly journals Twenty Years of Unrelated Donor Bone Marrow Transplantation for Pediatric Acute Leukemia Facilitated by the National Marrow Donor Program

2008 ◽  
Vol 14 (9) ◽  
pp. 16-22 ◽  
Author(s):  
Margaret L. MacMillan ◽  
Stella M. Davies ◽  
Gene O. Nelson ◽  
Pintip Chitphakdithai ◽  
Dennis L. Confer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Marrow Transplantation ◽  
Unrelated Donor ◽  
Donor Bone Marrow
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