Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation

Hart, Christina; Klatt, Sabine; Barop, Johann; Müller, G.; Schelker, Roland Christian; Holler, Ernst; Huber, Elisabeth; Herr, Wolfgang; Grassinger, Jochen

doi:10.3324/haematol.2016.146811

Cited by 25 publications

(19 citation statements)

References 46 publications

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“…Previous studies suggested that enlarged spleen is related to the low rate of engraftment [37,38], which probably resulted from 2 factors. On one hand, the infused CD34 + cells could be sequestered by the spleen which leads to a delayed homing and hypocellular bone marrow [39]; on the other hand, the newly generated blood cells could easily get trapped and destroyed by the enlarged spleen [40]. Splenectomy or spleen irradiation might be an option, but these treatments remain controversial.…”

Section: Discussionmentioning

confidence: 99%

Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Zhao

Gao

Shi

et al. 2019

Biology of Blood and Marrow Transplantation

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for both malignant and nonmalignant hematologic disorders. However, primary poor graft function (PGF) is a serious early complication of allo-HSCT that leads to a poor outcome. Little is known about the characteristics, incidence, and risk factors of primary PGF occurring after allo-HSCT. Here we performed a 1:4 ratio nested case-control study in 830 patients who underwent allo-HSCT between April 2013 and November 2018 at our center. Twenty-four patients (14 males and 10 females; average age, 35.79 years; range, 17 to 53 years) developed primary PGF. On univariate and multivariate analyses, a CD34 + cell dose <5 £ 10 6 /kg (P = .003), a serum ferritin (SF) level >2000 ng/mL (P = .008), and splenomegaly (P = .039) were identified as 3 independent risk factors for primary PGF. After a median follow-up of 7.5 months (range, 1 to 48 months), only 5 patients (20.8%) survived. The survival rate of patients with primary PGF was significantly lower than that of patients with good graft function (GGF) (1-year overall survival, 25.0% versus 90.6%; P < .001). Cox regression analysis suggested that PGF and high SF level were strongly associated with rapid death in these patients. In conclusion, allo-HSCT recipients with a low CD34 + cell dose in their graft and exhibiting a high SF level and splenomegaly should be monitored for the development of primary PGF after allo-HSCT, and effective therapies need to be explored.

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Section: Discussionmentioning

confidence: 99%

Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Zhao

Gao

Shi

et al. 2019

Biology of Blood and Marrow Transplantation

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“…Splenomegaly may be associated with a lower incidence of engraftment [26,36], but this remains controversial [25,37,38]. Engraftment failure after HSCT for myelofibrosis patients is supposed to be caused by early pooling of hematopoietic stem cells in the spleen [39]. JAK inhibitor therapy results in reduction of splenomegaly and may contribute to engraftment [40].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Outcomes of Allogeneic Transplantation for Primary Myelofibrosis among Hematopoietic Stem Cell Source Groups

Murata

Takenaka

Uchida

et al. 2019

Biology of Blood and Marrow Transplantation

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The choice of alternative donor is a major issue in allogeneic hematopoietic stem cell transplantation (HSCT) for patients with primary myelofibrosis (PMF) without an HLA-matched related donor. We conducted this retrospective study using the Japanese national registry data for 224 PMF patients to compare the outcomes of first allogeneic HSCT from HLA-matched related donor bone marrow (Rtd-BM), HLA-matched related donor peripheral blood stem cells (Rtd-PB), HLA-matched unrelated donor bone marrow (UR-BM), unrelated umbilical cord blood (UR-UCB), and other hematopoietic stem cell grafts. Nonrelapse mortality (NRM) rates at 1 year after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantations were 16%, 36%, 30%, 41%, and 48%, respectively. Multivariate analysis identified UR-UCB transplantation, other transplantation, frequent RBC transfusion before transplantation, and frequent platelet (PLT) transfusion before transplantation as predictive of higher NRM. Relapse rates at 1 year after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantation were 14%, 17%, 11%, 14%, and 15%, respectively. No specific factor was associated with the incidence of relapse. Overall survival (OS) at 1 and 4 years after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantation were 81% and 71%, 58% and 52%, 61% and 46%, 48% and 27%, and 48% and 41%, respectively. Multivariate analysis identified older patient age, frequent RBC transfusion before transplantation, and frequent PLT transfusion before transplantation as predictive of lower OS. In conclusion, UR-UCB transplantation, as well as UR-BM transplantation, can be selected for PMF patients without an HLA-identical related donor. However, careful management is required for patients after UR-UCB transplantation because of the high NRM. Further studies including more patients after HLA-haploidentical related donor and HLA-mismatched unrelated donor transplantation would provide more valuable information for patients with PMF when making decisions regarding the choice of alternative donor.

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“…The contribution of spleen to HSC transplantation and hematopoietic rescue in humans remains contentious although several findings are relevant. Spleen size in patients with myelofibrosis has been found to have a negative effect on the engraftment efficiency of CD34 + cells following transplantation . HSC engraftment is also delayed in patients with splenomegaly and in children with hypersplenism .…”

Section: Spleen Involvement In Hsc Transplantationmentioning

confidence: 99%

“…HSC engraftment is also delayed in patients with splenomegaly and in children with hypersplenism . Early pooling of CD34 + HSCs in spleen, coupled with a defect in bone marrow homing, has been shown to reduce the engraftment of HSCs into the bone marrow following transplantation and may be the cause of graft failure . Reduction in spleen size is thought to improve HSC homing to bone marrow, and partial or total splenectomy can improve the rate of HSC engraftment .…”

Section: Spleen Involvement In Hsc Transplantationmentioning

confidence: 99%

Targeting the Spleen as an Alternative Site for Hematopoiesis

et al. 2019

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Bone marrow is the main site for hematopoiesis in adults. It acts as a niche for hematopoietic stem cells (HSCs) and contains non‐hematopoietic cells that contribute to stem cell dormancy, quiescence, self‐renewal, and differentiation. HSC also exist in resting spleen of several species, although their contribution to hematopoiesis under steady‐state conditions is unknown. The spleen can however undergo extramedullary hematopoiesis (EMH) triggered by physiological stress or disease. With the loss of bone marrow niches in aging and disease, the spleen as an alternative tissue site for hematopoiesis is an important consideration for future therapy, particularly during HSC transplantation. In terms of harnessing the spleen as a site for hematopoiesis, here the remarkable regenerative capacity of the spleen is considered with a view to forming additional or ectopic spleen tissue through cell engraftment. Studies in mice indicate the potential for such grafts to support the influx of hematopoietic cells leading to the development of normal spleen architecture. An important goal will be the formation of functional ectopic spleen tissue as an aid to hematopoietic recovery following clinical treatments that impact bone marrow. For example, expansion or replacement of niches could be considered where myeloablation ahead of HSC transplantation compromises treatment outcomes.

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Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation

Cited by 25 publications

References 46 publications

Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Comparison of Outcomes of Allogeneic Transplantation for Primary Myelofibrosis among Hematopoietic Stem Cell Source Groups

Targeting the Spleen as an Alternative Site for Hematopoiesis

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