Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia

Yamamoto, Hisashi; Kato, Daisuke; Uchida, Naoyuki; Ishiwata, Kiichi; Araoka, Hideki; Takagi, Shinsuke; Nakano, Nobuaki; Tsuji, Motomu; Asano‐Mori, Yuki; Matsuno, Naofumi; Masuoka, Kazuhiro; Izutsu, Koji; Wake, Atsushi; Yoneyama, Akio; Makino, Shigeyoshi; Taniguchi, Satoshi

doi:10.1182/blood-2010-08-295832

Cited by 46 publications

(29 citation statements)

References 16 publications

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“…Unrelated cord blood transplantation has extended the availability of treatment in patients with SAA in an absence of a suitable donor, but most reports have shown a poor outcome and high incidence of GF. 18 However, Yamamoto et al 19 reported sustained engraftment in 11 of 12 patients with SAA who received unrelated cord blood transplantation with the FLU+MEL+low-dose TBI regimen. Taken together, the FLU+MEL+ATG+low-dose TBI regimen may be the most promising regimen for patients who receive a second HSCT for SAA.…”

Section: Discussionmentioning

confidence: 99%

Second allogeneic hematopoietic stem cell transplantation in children with severe aplastic anemia

Kudo

Muramatsu

Yoshida³

et al. 2015

Bone Marrow Transplant

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The outcome of 55 children with severe aplastic anemia (SAA) who received a second hematopoietic stem cell transplantation (HSCT) was retrospectively analyzed using the registration data of the Japanese Society for Hematopoietic Cell Transplantation. The 5-year overall survival (OS) and failure-free survival (FFS) after the second transplantation were 82.9% (95% confidence interval (CI), 69.7-90.8)) and 81.2% (95% CI, 67.8-89.4), respectively. FFS was significantly better when the interval between the first and second transplantation was 460 days (88.9%; 95% CI, 73.0-95.7) than when it was ⩽ 60 days (61.4%; 95% CI, 33.3-80.5; P = 0.026). All 12 patients who were conditioned with regimens containing fludarabine and melphalan were alive with hematopoietic recovery. These findings justify the recommendation of a second HSCT for children with SAA who have experienced graft failure after first HSCT.

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Section: Discussionmentioning

confidence: 99%

Second allogeneic hematopoietic stem cell transplantation in children with severe aplastic anemia

Kudo

Muramatsu

Yoshida³

et al. 2015

Bone Marrow Transplant

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“…57,58 In contrast, experience from larger cohorts in retrospective analyses indicate that overall survival is not as favorable as in pilots, at approximately 40% at 2 to 3 years. [59][60][61] Graft rejection and poor immune reconstitution continue to limit the success of UC HSCT.…”

Section: Alternative Donor Hsctmentioning

confidence: 97%

How I treat acquired aplastic anemia

Scheinberg

Young

2012

Blood

362

333

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Survival in severe aplastic anemia (SAA) has markedly improved in the past 4 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive biologics and drugs, and supportive care. However, management of SAA patients remains challenging, both acutely in addressing the immediate consequences of pancytopenia and in the long term because of the disease's natural history and the consequences of therapy. Recent insights into pathophysiology have practical implications. We review key aspects of differential diagnosis, considerations in the choice of firstand second-line therapies, and the management of patients after immunosuppression, based on both a critical review of the recent literature and our large personal and research protocol experience of bone marrow failure in the Hematology Branch of the National Heart, Lung, and Blood Institute. (Blood. 2012;120(6): 1185-1196) IntroductionUntil the 1970s, severe aplastic anemia (SAA) was almost uniformly fatal, but in the early 21st century most patients can be effectively treated and can expect long-term survival. Nevertheless, making a diagnosis and selecting among treatment options are not straightforward, and both physicians and patients face serious decision points at the outset of their disease to years after its presentation. We summarize our approach to SAA, with recommendations based on decades of experience in the clinic as well as a critical review of the literature. Unfortunately, as a rare disease, there are few large trials of any kind and even fewer randomized controlled studies, which usually provide the best evidence to guide practice in the clinic. Pathophysiology as basis of diagnosis and treatmentThe pathophysiology responsible for marrow cell destruction and peripheral blood pancytopenia has itself been inferred from the results of treatment in humans, with substantial in vitro and animal model support. The reader is referred to more didactic textbook chapters and formal reviews on these topics. [1][2][3][4] The success of HSCT in restoring hematopoiesis in SAA patients implicated a deficiency of HSCs. Hematologic improvement after immunosuppressive therapy (IST), initially in the context of rejected allogeneic grafts and then in patients receiving only IST, implicated the immune system in destruction of marrow stem and progenitor cells. Immune-mediated marrow failure can be modeled in the mouse by the "runt" version of GVHD, with HSC depletion and hematopoietic failure induced by infusion of lymphocytes mismatched at major or minor histocompatibility loci. 5,6 Genetics influences both the immune response and its effects on the hematopoietic compartment. There are histocompatibility gene associations with SAA, 7 and some cytokine genes may be more readily activated in patients because of differences in their regulation, as suggested by polymorphisms in promoter regions. 8 An inability to repair telomeres and to maintain the marrow's regenerative capacity, resulting from mutations in the complex of genes responsible for tel...

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“…Yoshimi et al 15 also found that the number of infused TNC and CD34 þ cells had no impact on the engraftment and survival with the minimum of 2 Â 10 7 /kg TNCs infused. Lately, Yamamoto et al 22 have reported promising results of engraftment and survival in CBT for SAA patients using a reduced intensity conditioning regimen of 125 mg/m 2 FLU, 80 mg/m 2 melphalan and 4 Gy fractionated TBI with a median infused TNC 2.5 Â 10 7 /kg. In our series, the minimum TNC at infusion was 2.34 Â 10 7 /kg, all patients who had no multiple transfusion exposure before transplant experienced engraft failure.…”

Section: Discussionmentioning

confidence: 99%

Unrelated cord blood transplantation for newly diagnosed patients with severe acquired aplastic anemia using a reduced-intensity conditioning: high graft rejection, but good survival

Liu

et al. 2012

Bone Marrow Transplant

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We report a single-center experience in treating 18 consecutive patients with severe aplastic anemia (SAA) who received unrelated cord blood transplantation (CBT). The median age was 17 years (range 5 --61 years). Sixteen cases received a reducedintensity regimen composed of CY (total dose1200 mg/m 2 ), rabbit antithymocyte globulin (ATG, total dose 30 mg/kg) and fludarabine (FLU, total dose 120 mg/m 2 ). CYA and mycophenolate mofetil were used as GVHD prophylaxis. Two patients were not evaluable for engraftment because of early death on day þ 21 and þ 22. Only one of the sixteen cases achieved engraftment, but experienced secondary graft failure 3 months post transplantation. Fifteen patients experienced primary graft rejection, but all of them acquired autologous recovery. The 3-month and 6-month cumulative incidence of response was 56% and 81%, respectively. So far, 16 patients have survived for 330 --1913 days (median, 750 days) after transplantation. The probability of OS at 2 years was 88.9%. Our data indicate that CBT for newly diagnosed SAA using no irradiation but FLU and ATG-based conditioning still seems to inevitably lead to the high risk of rejection, but may facilitate autologous recovery and improve survival with low risk of transplant-related mortality.

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Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia

Abstract: We retrospectively analyzed 12 consecutive adult severe aplastic anemia patients who received unrelated umbilical cord blood transplantation after a reducedintensity conditioning regimen (RI-UCBT).

Cited by 46 publications

References 16 publications

Second allogeneic hematopoietic stem cell transplantation in children with severe aplastic anemia

Second allogeneic hematopoietic stem cell transplantation in children with severe aplastic anemia

How I treat acquired aplastic anemia

Unrelated cord blood transplantation for newly diagnosed patients with severe acquired aplastic anemia using a reduced-intensity conditioning: high graft rejection, but good survival

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