Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy

Barker, Juliet N.; Weisdorf, Daniel J.; DeFor, Todd E.; Blazar, Bruce R.; McGlave, Philip B.; Miller, Jeffrey S.; Verfaillie, Catherine M.; Wagner, John E.

doi:10.1182/blood-2004-07-2717

Cited by 795 publications

(719 citation statements)

References 24 publications

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“…In a study of 21 patients treated with a nonmyeloablative approach, Ballen et al [25] found that TRM at day 100 post-transplant was only 14% and the occurrence of severe acute GvHD remained low. As in the study by Barker et al [24], all of the patients engrafted with 1 UCB unit by 3 months posttransplantation. Relapse rates among these patients were low suggesting that the GvL effect was present despite the low rates of GvHD.…”

Section: Transplantation With Ucb : Clinical Studiesmentioning

confidence: 92%

“…Barker et al [18] reported the use of double UCB transplantation in the context of a clinical trial designed to evaluate the efficacy of reduced-intensity conditioning with UCB transplantation. This initial report was followed by a study devoted exclusively to evaluating the safety of double UCB transplantation for hematological malignancy in adults [24]. Following myeloablative conditioning, 23 patients with high-risk hematologic malignancy were infused with 2 partially HLA-matched UCB units containing a median cell dose of 3.5 × 10 7 nucleated cells/kg.…”

Section: Transplantation With Ucb : Clinical Studiesmentioning

confidence: 99%

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Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Brown

Boussiotis

2008

Clinical Immunology

150

111

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Allogeneic stem cell transplantation has continued to evolve as a common procedure for the treatment of hematological malignancies and bone marrow failure. Donor bone marrow and mobilized peripheral stem cells are routinely employed for the reconstitution of immune function in leukemia and lymphoma patients following radiation and/or chemotherapy. Unfortunately, only 30% of patients have an HLA identical sibling donor and the identification of matched unrelated donors, particularly for minorities, can present an exceptional challenge. The transplantation of umbilical cord blood (UCB) represents the most recent strategy to expand the potential donor pool while maintaining an acceptable level of treatment related complications. First utilized in children, UCB transplantation permits a higher degree of HLA disparity while demonstrating a reduction in the incidence and severity of graft versus host disease (GvHD) compared to previous transplantation modalities. Despite the apparent decrease in GvHD, relapse rates remain comparable to transplantation with bone marrow or mobilized peripheral blood suggesting a strong graft versus leukemia/lymphoma (GvL) effect. However, several issues complicate the use of UCB transplantation and its extension to the treatment of adults. Many infections that afflict transplant patients are particularly frequent and more severe in the context of UCB transplantation. UCB T cells are naïve and therefore display less proliferation and IFN-γ production in response to cognate antigen and also appear to demonstrate defects in signal transduction mechanisms. In addition, UCB contain T regulatory cells (Treg) with more potent suppressor function than adult Treg. Furthermore, adult patients often require more total cells and CD34+ progenitors for transplantation than a single UCB unit can provide. Thus, strategies to expand selected subpopulations from UCB and the use of multiunit transplantation are areas of active research. This review will provide a condensed summary of the clinical history of UCB transplantation and emphasize the advantages and disadvantages of this approach to hematological malignancies in comparison to other methods of hematopoietic stem cell transplantation. Subsequently, it will mainly focus on the current challenges to immune reconstitution presented by UCB transplantation, recent research into their cellular and molecular mechanisms, and experimental approaches to overcome them.

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Section: Transplantation With Ucb : Clinical Studiesmentioning

confidence: 92%

Section: Transplantation With Ucb : Clinical Studiesmentioning

confidence: 99%

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Brown

Boussiotis

2008

Clinical Immunology

150

111

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“…3 According to published reports, for most patients the time to ANC recovery after double CBT, both with standard and reduced-intensity conditioning, is not significantly shorter than that for single unit CBT and usually results from the exclusive and unpredictable engraftment of one of the units. [22][23][24][25] The benefit of double CBT seems to result from a higher chance for engraftment and full CB chimerism, on top of other possible undetermined effects, immunological or otherwise, that could also influence the prevalence of the engrafting unit. We do not have data indicative of the mechanism underlying the final replacement of the TPD graft by the CBT in the dual CBT/TPD-MHSC model.…”

Section: Evaluable Patients 55mentioning

confidence: 99%

Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor

Bautista

Cabrera

Regidor

et al. 2008

Bone Marrow Transplant

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This open label clinical study provides updated evaluation of the strategy of single unit cord blood transplants (CBTs) with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC). Fifty-five adults with high-risk hematological malignancies, median age 34 years (16-60 years) and weight 70 kg (43-95 kg), received CBTs (median 2.39 Â 10 7 total nucleated cell (TNC) per kg and 0.11 Â 10 6 CD34 þ per kg) and TPD-MHSC (median 2.4 Â 106 CD34 þ per kg and 3.2 Â 10 3 CD3 þ per kg). Median time to ANC and to CB-ANC 40.5 Â 10 9 /l as well as to full CB-chimerism was 10, 21 and 44 days, with maximum cumulative incidences (MCI) of 0.96, 0.95 and 0.91. Median time to unsupported platelets 420 Â 10 9 /l was 32 days (MCI 0.78). MCI for grades I-IV and III-IV acute GVHD (aGVHD) were 0.62 and 0.11; 12 of 41 patients (29%) who are at risk developed chronic GVHD, becoming severely extensive in three patients. Relapses occurred in seven patients (MCI ¼ 0.17). The main causes of morbi-mortality were post-engraftment infections. CMV reactivations were the most frequent, their incidence declining after the fourth month. Five-year overall survival and disease-free survival (Kaplan-Meier) were 56 % and 47% (63% and 54% for patients p40 years). In conclusion, CBT with single units of relatively low cell content and 0-3 HLA mismatches is feasible as a first choice option for adult patients who lack a readily available adequate adult donor.

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“…Currently, there is little data to guide a clinician's management decisions. In a case series, eight of the 26 subjects with mild or moderate hemophilia complicated by an inhibitor underwent ITI; two were successful, two were unsuccessful, and four were partially successful [2]. In a systematic review of the literature, 12 of the 16 patients with mild or moderate hemophilia responded to rituximab for treatment to eradicate the inhibitor [3].…”

Section: Lettersmentioning

confidence: 99%

“…The use of a second unit helps ensure engraftment in larger adults and those with comorbidities, even though only one unit engrafts in most patients [1,2]. Herein, we present the clinical and laboratory characteristics of a patient who developed donor-derived myelodysplastic syndrome (ddMDS) after double umbilical cord-blood transplantation (dUCB HSCT).…”

mentioning

confidence: 99%

An unusual case of donor‐derived myelodysplastic syndrome following double‐unit umbilical cord blood transplantation in acute lymphoblastic leukemia

et al. 2012

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Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy

Cited by 795 publications

References 24 publications

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor

An unusual case of donor‐derived myelodysplastic syndrome following double‐unit umbilical cord blood transplantation in acute lymphoblastic leukemia

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