Megadose transplantation of purified peripheral blood CD34+progenitor cells from HLA-mismatched parental donors in children

Handgretinger, Rupert; Klingebiel, Thomas; Lang, Peter; Schumm, Michael; Neu, S; Geiselhart, A; Bader, Peter; Schlegel, Paul G.; Greil, Johann; Stachel, Daniel; Herzog, Richard; Niethammer, D.

doi:10.1038/sj.bmt.1702996

Cited by 263 publications

(215 citation statements)

References 26 publications

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“…4,17,18 However, combining CD34-selected haploidentical cells with a fully myeloablative conditioning regimen for patients with malignancy has been more fully explored in adult patients, 1,2 though some pediatric reports exist. [19][20][21] Fewer reports have focused on children with life-threatening nonmalignant diseases, [21][22][23] where the use of UCB stem cells predominates because many children are an appropriate size to receive the small cell dose in an UCB unit. For larger children and adults, two UCB units can be combined.…”

Section: Discussionmentioning

confidence: 99%

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

Dvorak

Horn

et al. 2012

Bone Marrow Transplant

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We conducted a prospective phase II trial utilizing the CliniMACs system to perform CD34 þ -cell selection of PBSCs from haploidentical donors to evaluate engraftment and hematoimmunological reconstitution. In total, 21 children with hematological malignancies or nonmalignant conditions underwent conditioning with 1200 cGy TBI, thiotepa, fludarabine and Thymoglobulin. Patients received megadoses of CD34 þ cells (median: 22 Â 10 6 /kg) with a fixed dose of 3 Â 10 4 /kg CD3 þ cells/kg, and engraftment occurred in 90% with prompt recovery of neutrophils and platelets. Grade II acute GVHD (aGVHD) was seen in 32% (95% confidence interval (CI), 15-54%) of evaluable patients, there was no grade III-IV aGVHD, and chronic extensive GVHD was seen in 35% (95% CI, 17-59%) of patients. The estimated 2-year EFS was 62% (95% CI, 48-83%) with a median survivor follow-up of 49 months (range: 18-119 months). Patients with nonmalignant diseases had an estimated 2-year EFS of 100% (95% CI, 56-100%) and patients with malignancies in remission had an estimated 2-year EFS of 56% (95% CI, 22-89%). Megadose CD34 þ cells with a fixed CD3 þ cell dose from haploidentical related donors resulted in good outcomes for pediatric patients with nonmalignant diseases and those with malignant diseases transplanted in remission.

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Section: Discussionmentioning

confidence: 99%

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

Dvorak

Horn

et al. 2012

Bone Marrow Transplant

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“…This concept has proven to be highly efficacious in preventing graft rejection for transplantation across HLA barriers (haploidentical transplantation). 5,23,24 However, it is important to state that the German multicenter protocol MPS-HCT 2005 includes the following algorithm for selecting a graft:…”

Section: Discussionmentioning

confidence: 99%

Allogeneic blood SCT for children with Hurler's syndrome: results from the German multicenter approach MPS-HCT 2005

Sauer

Meissner

Fuchs

et al. 2008

Bone Marrow Transplant

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Hurler's syndrome is an inborn error of mucopolysaccharide metabolism leading to premature death in childhood. Allogeneic hematopoietic SCT can achieve long-term survival by correcting the enzymatic deficiency. In an attempt to improve long-term engraftment and to reduce regimen-related toxicity (RRT), a prospective multicenter approach was initiated in Germany using a fludarabinebased radiation-free preparative regimen. Between 2001 and 2008, 12 children were enrolled. Median age at SCT was 14 months (range, 4-31 months). The conditioning regimen contained fludarabine, BU, melphalan and antithymocyte globulin. CD34 positively selected PBSC were used in 10 children with a matched unrelated donor. Median cell dose was 24.6 Â 10 6 CD34 þ cells per kg (range 10.0-54.8). Two children with a matched sibling donor received non-manipulated BM. Donor lymphocyte infusions were given in 6/12 children for mixed hematopoietic chimerism. At a median follow-up of 29 months (range 2-85 months), all children engrafted and have either stabilized or improved neurological function. In total, 12/12 patients showed donor-derived engraftment with 9/12 having full and 3/12 having mixed hematopoiesis. One developed acute GVHD Xgrade II. RRT Xgrade II was observed in two patients.

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“…The positive selection of CD34 1 stem cells was introduced as an efficient large-scale clinical indirect method for T cell depletion and a number of clinical studies using peripheral CD34 1 stem cells were performed in adults and children [4,25]. Although CD34 1 positive selection methods have widely been used to indirectly deplete T and B cells from mobilized peripheral stem cell grafts, negative T cell-depletion strategies might offer some advantages in overcoming the HLA barrier with RIC while maintaining an effective graft-versus-malignancy effect.…”

Section: Reduced-intensity Conditioning (Ric) and Cd3/19 Depletion: Amentioning

confidence: 99%

Preservation of Immune Repertoire by Selective Depletion of Haploidentical Grafts

Guinan

Luzmik

Handgretinger

et al. 2010

Biology of Blood and Marrow Transplantation

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Megadose transplantation of purified peripheral blood CD34+progenitor cells from HLA-mismatched parental donors in children

Cited by 263 publications

References 26 publications

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

Allogeneic blood SCT for children with Hurler's syndrome: results from the German multicenter approach MPS-HCT 2005

Preservation of Immune Repertoire by Selective Depletion of Haploidentical Grafts

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