Outcomes of patients diagnosed with chronic lymphocytic leukemia after allogeneic hematopoietic stem cell transplantation: results from a tertiary care center

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) may potentially cure patients with chronic lymphocytic leukemia (CLL) and Richter’s transformation (CLL-RT) or CLL without RT, but the impact of novel agents on HSCT is unclear. CLL-RT patients have a grave prognosis, and their outcomes after HSCT are uncertain. We conducted a retrospective analysis of all 58 CLL patients, including 23 CLL-RT patients, who underwent reduced intensity conditioning (RIC) HSCT at Memorial Sloan Kettering Cancer Center (New York, NY) between September 2006 and April 2017. With a median follow-up of 68 months (range, 24-147 months), 5-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 28%-56%), and overall survival (OS) was 58% (95% CI, 48%-74%). The 1-year graft-versus-host disease/relapse-free survival (GRFS) was 38% (95% CI, 25%-50%). Patients with CLL-RT and CLL patients without RT had comparable outcomes. In both cohorts, treatment-sensitive response and ≤3 previous lines of therapy produced superior PFS and OS. Outcomes were agnostic to adverse cytogenetic and molecular features. Novel agents did not have a negative impact on HSCT outcomes. Total body irradiation (TBI)-containing RIC yielded inferior PFS, OS, and GRFS. CLL-RT patients older than age 55 years who had an HSCT Comorbidity Index score of ≥2 demonstrated inferior OS. This study, which is the largest series of RIC-HSCT for patients with CLL-RT, provides evidence supporting RIC-HSCT in early remission courses for patients with CLL-RT and poor-risk CLL patients. TBI-containing RIC should be considered with caution.

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Reversal of Acquired von Willebrand Disease after Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with High Risk Chronic Lymphocytic Leukemia.

Blood ◽

10.1182/blood.v104.11.4014.4014 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4014-4014 ◽

Cited By ~ 1

Author(s):

Christian Langer ◽

Martin Griesshammer ◽

Donald Bunjes ◽

Ulrich Budde ◽

Martin Gruenewald ◽

...

Keyword(s):

Stem Cell ◽

Chronic Lymphocytic Leukemia ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Lymphocytic Leukemia ◽

Hematopoietic Stem ◽

Binet Stage ◽

Von Willebrand

Abstract Acquired von Willebrand (AvWD) disease is a relatively rare bleeding disorder and since the initial description, fewer than 300 cases of AvWD have been reported. The most frequently observed association is with dysproteinemias such as monoclonal gammopathy of undetermined significance (MGUS) and plasma cell proliferative disorders such as Waldenstroem macroglobulinemia and multiple myeloma. Other hematological diseases associated with AvWD have been reported including lymphoproliferative and myeloproliferative disorders. We report the case of a 59 year old male patient with an AvWD associated with a chronic lymphocytic leukemia. In November 2000 this patient was diagnosed with a B cell chronic lymphocytic leukemia (CLL). Because of an initial Binet-Stage A no specific therapy was initiated. In October 2003 the CLL progressed to Binet-Stage B and molecular examinations revealed an unfavorable risk profile with a 11q22.3-q23.1 deletion and an unmutated IgVH gene status. Because of the presence of an HLA-identical brother the patient was enrolled into a pilot study of allogeneic stem cell transplantation following conditioning with fludarabine and cyclophosphamid in patients with high-risk chronic lymphocytic leukemia. Four cycles of fludarabine and cyclophosphamide were given prior to allogeneic stem cell transplantation and induced a partial remission. Since 2000 the patient reported a new clinical bleeding tendency, presenting mainly as frequent epistaxis. Further laboratory investigations showed a prolonged activated partial thromboplastin time (50 sec.) and a reduced plasma von Willebrand factor (vWF) antigen and vWF activity of 6% and 2%, respectively. This was accompanied by a reduced Factor VIII activity of 14% (factor IX-, XI-, XII- activity > 100%, respectively; lupus anticoagulant assay negative; immunofixation negativ). A vWF multimer analysis showed selective decrease in the high-molecular-weight multimers as seen in type II congenital vWD. The reduced intensity conditioning (RIC) regimens consisted the following combination: Fludarabine 30mg/m² /d (=150mg/m² total dose) and Cyclophosphamide 500mg/m² /d (=2500mg/m² total dose) (day -7 through day -3), GVHD prophylaxis with Cyclosporin A (CsA) and mycophenolate mofetil (MMF). A therapeutic trial of desmopressin (DDAVP) was insufficient and therefore a continuous infusion of the factor VIII/vWF concentrate (Haemate® P; Aventis Behring) was administered from the start of conditioning until platelet recovery. Under this regimen no bleeding complication was observed, neither spontaneously nor during intensive procedures. In accordance with previous reports of replacement therapy in AvWD we observed a shortened half-life of the vWF. On day 30 after allogenic hematopoietic stem cell transplantation we observed for the first time a normalization of the activated partial thromboplastin time followed by a gradual increase of the vWF antigen and activity. On day 60 we were able to document the normalization of both the vWF antigen and activity and the vWF multimer analysis. This nomalisation was coincident with the establishment of a complete donor chimerism for the first time. We therefore believe that this case shows a form of AvWD associated with chronic lymphocytic leukemia and its reversal by treatment of the underlying disease by allogeneic hematopoietic stem cell transplantation. Figure Figure

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