Autologous bone marrow transplantation with 4‐hydroperoxycyclophosphamide‐purged marrow for acute lymphoblastic leukemia

Gonzales‐Chambers, Rowena; Przepiorka, Donna; Shadduck, Richard K.; Borochovitz, Dennis; Bloom, Éric; Colvin, O. Michael; Mangan, Kenneth F.; Rosenfeld, Craig S.

doi:10.1002/mpo.2950190303

Cited by 8 publications

(1 citation statement)

References 24 publications

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“…The remaining patients were conditioned with IV Cy (50 mg/kg/day) for 4 days in the alloidentical transplant patients and for 2 days in the unrelated donor transplant patients. This was followed by 300 CGy total body irradiation (TBI) daily for 4 days [21].…”

Section: Preparative Regimensmentioning

confidence: 99%

Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation

et al. 1998

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Our objectives were to measure and compare plasminogen activator inhibitor levels (PAI-1) in primary adult thrombotic thrombocytopenic purpura (TTP) and in secondary TTP associated with bone marrow transplantation (BMT)-TTP. PAI-1 antigen levels were measured by an enzyme linked immunosorbent assay on platelet poor plasma samples obtained from patients at the time of diagnosis of the TTP disorder and from a group of normal volunteers. The samples were frozen at -70 degrees C. Patients with TTP secondary to bone marrow transplantation had their grade determined by percentage fragmented cells and lactate dehydrogenase levels. The primary TTP samples were contributed by investigators in the multi-institutional North American TTP Group, and the bone marrow transplant samples were obtained from an adult bone marrow transplant program. Nineteen patients with adult TTP, and 47 patients with bone marrow transplant-TTP were evaluated. Of the latter, 14 had Grade 2, 13 had Grade 3, and 20 had Grade 4 BMT-TTP. PAI-1 levels were elevated compared to control volunteers in both primary adult TTP and BMT-TTP, P < 0.001. Levels did not differ from normal in Grade 2 BMT-TTP (median = 16 ng/ml; quartiles = 9-20). PAI-1 levels were similar in primary TTP (median = 32 ng/ml; quartiles = 25-51) and Grade 3 BMT-TTP (median = 35 ng/ml; quartiles = 19-48 ng/ml), P = 0.7. However, PAI-1 levels were significantly higher in Grade 4 BMT-TTP (median = 83 ng/ml; quartiles = 60-143) than Grade 3 BMT-TTP, and primary TTP, P < 0.001. PAI-1 levels are high in primary TTP and secondary bone marrow transplant-TTP (Grades 3-4). In contrast, normal levels are seen in Grade 2 BMT-TTP, which is a self-limited disorder. Therefore, high PAI-1 levels may contribute to hypofibrinolysis in the pathogenesis of primary TTP and of moderate to severe TTP (Grades 3-4) following bone marrow transplantation.

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Section: Preparative Regimensmentioning

confidence: 99%

Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation

et al. 1998

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Plasma von Willebrand factor antigen (vWF:AG) and thrombomodulin (TM) levels in adult thrombotic thrombocytopenic purpura/hemolytic uremic syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM)

Zeigler

Andrews

et al. 1996

Am. J. Hematol.

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Endothelial damage is thought to be a contributing factor in the pathogenesis of Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS). The present studies measured two markers of endothelial cell stimulation and/or activation [von Willebrand Factor (vWF:Ag) and thrombomodulin (TM)] in patients with TTP/HUS disorders and compared them to controls. The patient groups consisted of adults with TTP/HUS, with (n = 13) and without (n = 14) peak Cr levels >2.0 mg/dl. Additionally, 52 patients with Bone Marrow Transplant-associated Thrombotic Microangiopathy (BMT-TM) following allogeneic BMT were evaluated. Both vWF:Ag and TM were elevated in all patient groups compared to controls. TTP/HUS patients with peak Cr >2.0 mg/dl had higher TM levels (P < 0.001) than did those with peak Cr levels below 2 mg/dl. However, thrombomodulin/ creatinine (TM/Cr) ratios did not differ in these two groups nor did they differ from controls. BMT-TM pts had higher vWF:Ag levels and higher TM/Cr ratios than controls and TTP/ HUS, P < 0.001. The median TM/Cr ratio in BMT-TM was 91 (range = 34-229) compared to 38 (range = 29-50) in controls, P < 0.001 and 38 (range = 6 to 156) in TTP/HUS, P < 0.001. Additionally both TM (P < 0.001) and TM/Cr (P < 0.02) were higher in patients with Grades 3 and 4 BMT-TM compared to those with Grade 2 BMT-TM. These results suggest that endothelial cell activation occurs in TTP/HUS and BMT-TM. Since TM/Cr ratios were higher in BMT-TM compared to TTP/HUS, these findings suggest that the mechanism of elevated TM in BMT-TM cannot be explained solely by altered renal excretion. Taken together, these findings strongly indicate a role of endothelial cell damage in BMT-TM.

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Apheresis in grade 4 bone marrow transplant associated thrombotic microangiopathy: A case series

Dua¹,

Zeigler²,

Shadduck³

et al. 1996

J. Clin. Apheresis

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Bone marrow transplant‐associated thrombotic microangiopathy (BMT‐TM) ranges in severity from a self‐limited to a fatal disorder. There has been no specific therapy for this condition. We have previously described a clinical grading system for BMT‐TM, based upon lactate dehydrogenase level (LDH) and percentage fragmented cells (FC) as follows: grade 0, normal or ↑ LDH and % FC ≤ 1.2%; grade 1, normal LDH and FC ≥ 1.3%; grade 2, ↑ LDH and FC = 1.3–4.8%; grade 3, ↑ LDH and FC = 4.9–9.6%; and grade 4, ↑ LDH and FC ≥ 9.7%. Patients with grade 4 BMT‐TM usually have fulminant disease and generally succumb. This study summarizes results using a variety of apheresis procedures in a series of 16 patients with grade 4 BMT‐TM. The apheresis procedures consisted of plasma exchange (with replacement with fresh frozen plasma or cryo‐poor plasma), and protein A immunoadsorption (PAI). The PAI exchanges were not done concurrently with plasma exchange procedures. Fifteen patients had undergone an allogeneic BMT and the 16th patient had undergone an autologous peripheral blood stem cell transplant. Half showed hematologic improvement with a downstaging of their TM to grades 1–3. All non‐responders died a median of 11 days following the onset of grade 4 BMT‐TM. The median survival in the responders was significantly (P = 0.001) increased to 218 days with three responders surviving more than 400 days following the onset of this severe complication. These results suggest a role for apheresis in the treatment of this lethal complication. Nevertheless grade 4 BMT‐TM represents a major complication of BMT; the median survival in this group of 16 patients with grade 4 BMT‐TM was only 31 days. © 1996 Wiley‐Liss, Inc.

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Autologous bone marrow transplantation with 4‐hydroperoxycyclophosphamide‐purged marrow for acute lymphoblastic leukemia

Cited by 8 publications

References 24 publications

Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation

Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation

Plasma von Willebrand factor antigen (vWF:AG) and thrombomodulin (TM) levels in adult thrombotic thrombocytopenic purpura/hemolytic uremic syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM)

Apheresis in grade 4 bone marrow transplant associated thrombotic microangiopathy: A case series

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