Takayoshi Tachibana

Clinical significance of minimal residual disease detected by multidimensional flow cytometry: Serial monitoring after allogeneic stem cell transplantation for acute leukemia

We analyzed minimal residual disease (MRD) by multidimensional flow cytometry (MFC) after allogeneic stem cell transplantation in 41 patients with acute myeloid leukemia (AML) (n=31) or acute lymphoblastic leukemia (ALL) (n=10). Aberrant antigen expression was compared with the results of quantitative PCR for WT1 mRNA (n=41) and leukemia-specific fusion transcripts (n=12; AML in seven, ALL in five). There was a significant correlation between detection of MRD by MFC and WT1 mRNA, as well as between MFC and fusion transcripts. Serial monitoring of MRD by the three techniques correlated in parallel to the clinical course in most of the patients, but three patients were only positive for WT1 during hematological remission. The overall survival time of patients with complete remission was significantly associated with the appearance of aberrant expression after transplantation. In conclusion, MFC is valuable for clinical management decisions after transplantation.

Pretransplant serum ferritin is associated with bloodstream infections within 100 days of allogeneic stem cell transplantation for myeloid malignancies

We retrospectively studied the association between iron overload and bloodstream infections (BSI) in the 100-day period following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia or myelodysplastic syndromes. Serum ferritin was measured before transplantation to evaluate iron overload. Of 114 adult patients who underwent transplantation between 2000 and 2008, 36 (32%) developed BSI. Of the 44 isolates, 63% were Gram-positive bacteria, 32% were Gram-negative bacteria, and 4% were fungi. The median time to the onset of the first BSI was day 28 (range day 0–95) after transplantation. Univariate analysis revealed a significantly higher incidence of BSI in the high (≥1,000 ng/ml, n = 57) than in the low (<1,000 ng/ml, n = 57) ferritin group (42.1 versus 21.1%, respectively, P = 0.017). Peripheral blood stem cell transplantation (PBSCT) (n = 23) showed a greater protective effect against BSI compared with bone marrow (n = 71) and cord blood (n = 20) transplantation. Pretransplantation serum ferritin (HR = 2.844, 95% CI: 1.180–6.859, P = 0.020) and PBSCT (HR = 0.135, 95% CI: 0.025–0.717, P = 0.019) were significant factors on multivariate analysis. In conclusion, pretransplantation serum ferritin significantly predicts BSI within the 100-day period after allo-HSCT.

Serum ferritin and disease status at transplantation predict the outcome of allo-SCT in patients with AML or myelodysplastic syndrome

Serum ferritin and disease status at transplantation predict the outcome of allo-SCT in patients with AML or myelodysplastic syndrome

Retrospective comparison of mobilization methods for autologous stem cell transplantation in multiple myeloma

The combination of cyclophosphamide and granulocyte‐colony stimulating factor (G‐CSF) has widely been used to mobilize hematopoietic stem cells (HSCs) for autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Recently, however, alternative approaches such as G‐CSF alone or etoposide followed by G‐CSF have been investigated. We, therefore, retrospectively analyzed the effects of these mobilization methods on collection yield and disease outcome in ASCT for MM. We reviewed 146 MM patients from whom we intended to collect stem cells. For mobilization, 67, 58, and 21 patients received cyclophosphamide and G‐CSF, etoposide and G‐CSF, and G‐CSF alone (including nonmyelosuppressive chemotherapy followed by G‐CSF), respectively. Among them, 136 achieved the target number of HSCs (at least 2 × 106/kg). Lower creatinine and higher albumin levels at diagnosis were significantly associated with successful yield. A lower number of infused HSCs, use of the etoposide for mobilization and high ISS were associated with delayed hematopoietic recovery. The mobilization methods did not significantly affect either the successful collection of more than 2 × 106 CD34‐positive cells/kg or PFS after ASCT. G‐CSF alone was sufficient for stem cell mobilization for a single ASCT. The optimal approach to collect HSCs in MM remains to be elucidated. Am. J. Hematol., 2010.

European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients

The Sokal and Hasford scores were developed in the chemotherapy and interferon era and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS) scoring system was developed. We performed a multicenter retrospective study to validate the effectiveness of each of the three scoring systems. The study cohort included 145 patients diagnosed with CML in chronic phase who were treated with imatinib. In the EUTOS low‐ and high‐risk groups, the cumulative incidence of complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (P = 0.797) and the 5‐year overall survival rate was 92.6% and 93.3% (P = 0.871), respectively. The cumulative incidence of CCyR at 12 months, 5‐year event‐free survival and 5‐year progression‐free survival were not predicted using the EUTOS scoring system. However, there were significant differences in both the Sokal score and Hasford score risk groups. In our retrospective validation study, the EUTOS score did not predict the prognosis of patients with CML in chronic phase treated with imatinib.

Pretransplant serum ferritin has a prognostic influence on allogeneic transplant regardless of disease risk.

Abstract A multicenter retrospective analysis of the influence of pretransplant serum ferritin (SF) was performed in 261 adult recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), including 159 patients with acute myeloid leukemia (AML), 66 with acute lymphoid leukemia (ALL) and 36 with myelodysplastic syndrome (MDS). Patients were divided into subgroups according to the pretransplant SF level [< 1000 ng/mL (low) vs. ≥ 1000 ng/mL (high)] and disease status at transplant. A high SF level was significantly associated with high disease risk (p = 0.041), but pretransplant SF and disease risk were independent significant prognostic factors for overall survival (OS), disease-free survival (DFS) and non-relapse mortality rate (NRM) on multivariate analysis. The high-SF group showed a worse outcome than the low-SF group among both standard-risk patients (OS: 54% vs. 64%, p = 0.043; DFS: 46% vs. 57%, p = 0.031) and high-risk patients (OS: 16% vs. 35%, p = 0.001; DFS: 15% vs. 34%, p = 0.001). In conclusion, a high SF at transplant adversely influences the outcome of allo-HSCT regardless of disease risk in patients with acute leukemia and MDS.

Successful treatment of a patient with adult T cell leukemia/lymphoma using anti-CC chemokine receptor 4 monoclonal antibody mogamulizumab followed by allogeneic hematopoietic stem cell transplantation

Adult T cell leukemia/lymphoma (ATLL) is an aggressive peripheral T cell neoplasm caused by human T cell lymphotropic/leukemia virus type-1 and has a poor prognosis. A new anti-CC chemokine receptor 4 monoclonal antibody (mogamulizumab) has been shown to be effective for ATLL. Although mogamulizumab is now available in Japan for patients with ATLL, the influence on allogeneic hematopoietic stem cell transplantation (HSCT) remains unclear. Here we report a woman with ATLL resistant to combination chemotherapy, who achieved complete remission following treatment with mogamulizumab and subsequently received allogeneic HSCT. The patient has remained in complete remission with controlled graft-versus-host disease. To our knowledge, this is the first report of an ATLL patient who received mogamulizumab treatment followed by allogeneic HSCT. We suggest that administration of mogamulizumab to chemotherapy-resistant patients with ATLL may improve their disease status before allogeneic HSCT and result in better survival.

The impact of the dose of natural killer cells in the graft on severe acute graft-versus-host disease after unrelated bone marrow transplantation

The impact of lymphocyte subpopulations on the outcome of bone marrow transplantation (BMT) remains uncertain. We investigated the relationship between the lymphocyte subpopulations of bone marrow grafts and the outcome of BMT. A total of 121 patients who underwent BMT at Kanagawa Cancer Center between 2000 and 2009 were analyzed. Grade III-IV acute graft-versus-host disease (GVHD) occurred in 35.9% of patients who received unrelated BMT with a CD56 cell dose ≤2.80×10(6)/kg versus only 9.7% of patients with a CD56 cell dose >2.80×10(6)/kg (P=0.017). In patients receiving related BMT, the cumulative incidence of grade III-IV acute GVHD did not differ significantly in relation to the CD56 cell dose. On multivariate analysis, older donor age (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03-1.15, P=0.004) and a high dose of CD56 cells (>2.80×10(6)/kg) (HR: 0.15, 95%CI: 0.03-0.92, P=0.040) were significant determinants of grade III-IV acute GVHD after unrelated BMT. None of the lymphocyte subpopulations had a significant impact on the outcome of transplantation, including the rate of neutrophil engraftment, relapse, relapse-free mortality, and overall survival. Our findings suggest that a high natural killer cell dose prevents severe acute GVHD after unrelated BMT, while sparing the graft-versus-leukemia effect.

A prognostic score with pretransplant serum ferritin and disease status predicts outcome following reduced-intensity SCT

A prognostic score with pretransplant serum ferritin and disease status predicts outcome following reduced-intensity SCT

Pre-SCT serum ferritin is a prognostic factor in adult AML, but not ALL.

Recent studies have suggested that pre-SCT iron overload is related to decreased survival after allo-SCT for hematologic malignancies.1, 2, 3, 4, 5 We previously reported that the pre-SCT serum ferritin level and the disease status at transplantation predict the outcome in patients with AML or myelodysplastic syndrome (MDS).6 This time, we investigated whether pre-SCT serum ferritin is a significant predictor of the prognosis in ALL patients.