Ayumi Numata

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.

Beta-2 microglobulin is a strong prognostic factor in patients with DLBCL receiving R-CHOP therapy

Useful prognostic markers for patients with diffuse large B cell lymphoma (DLBCL) have been reported. To identify which biomarker best predicts the prognosis of patients with DLBCL, we performed a retrospective study that included 319 DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy between 2003 and 2012. We assessed the prognostic significance of six biomarkers [lactate dehydrogenase, soluble interleukin-2 receptor, thymidine kinase activity, beta-2 microglobulin (B2M), C-reactive protein, and ferritin] and representative clinical characteristics using progression-free survival (PFS) as the endpoint. The study group included 181 men and 138 women with a median age of 63 years (range, 22-89 years). In a multivariate analysis, the serum B2M level most strongly correlated with PFS (hazard ratio, 2.11; P=0.04). In a univariate analysis, patients with serum B2M levels >1.75μg/mL (n=210) had a worse 3-year PFS rate (71.2%) than those with B2M levels <1.75μg/mL (n=109; 90.0%). Therefore, serum B2M level at the time of diagnosis is a useful prognostic indicator in DLBCL patients receiving R-CHOP.

Intrathecal methotrexate prophylaxis and central nervous system relapse in patients with diffuse large B-cell lymphoma following rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone

Abstract This study evaluated the efficacy of central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX) in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively studied 322 patients who achieved first complete remission (CR) after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The CNS prophylaxis consisted of four doses of IT-MTX (15 mg) with hydrocortisone (25 mg) administered after CR was achieved. Forty patients (12%) received CNS prophylaxis (group A) and 282 patients (88%) did not (group B). Three patients in group A (8%) and eight in group B (3%) experienced isolated CNS relapse during the first CR, although this difference was not statistically significant (p = 0.14). Ten of 11 CNS relapses occurred in the brain parenchyma with (n = 3) or without (n = 7) leptomeningeal involvement, and the remaining patient had exclusive leptomeningeal involvement. In patients with DLBCL attaining CR after R-CHOP, IT-MTX administration was insufficient to prevent CNS relapse.

Cytomegalovirus Pneumonia after Anti-CC-chemokine Receptor 4 Monoclonal Antibody (Mogamulizumab) Therapy in an Angioimmunoblastic T-cell Lymphoma Patient.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma. A 63-year-old man was diagnosed with AITL. He received 6 cycles of CHOP therapy, but showed progressive disease. Subsequently, he received ESHAP chemotherapy; however, it was not effective. He received mogamulizumab (an anti-CCR4 monoclonal antibody). After 4 cycles, his respiratory condition worsened and he was diagnosed with cytomegalovirus (CMV) pneumonia. Despite antiviral and antibiotic therapy, he died. We speculate that the combination of progressive lymphoma with mogamulizumab and chemotherapy likely caused CMV pneumonia. Because mogamulizumab therapy causes immunosuppression, if CMV pneumonia is suspected, then rapid treatment should be initiated.

Prognostic significance of serum beta-2 microglobulin level in Hodgkin lymphoma treated with ABVD-based therapy

AbstractnThe levels of serum beta-2 microglobulin (β2MG) are determined mainly from lymphoid tissue. To examine its prognostic value in Hodgkin lymphoma (HL), we conducted a retrospective analysis. We analyzed 67 patients with HL diagnosed and treated at seven institutes of the Yokohama City University Hematology Group between 1998 and 2011. The patients included 40 males and 27 females with a median age of 41xa0years (range 16–81xa0years). The HL subtypes were nodular sclerosis classical HL in 37 patients, mixed cellular classical HL in 23, lymphocyte-rich classical HL in 6, and nodular lymphocyte-predominant HL in 1. The 4-year overall survival (OS) rate of all 67 patients was 89xa0%. Patients with β2MG levels ≥2.5xa0mg/L (nxa0=xa018) showed inferior progression-free survival (PFS; 4-year PFS rate, 42xa0%) and inferior OS (4-year OS rate, 60xa0%) compared to patients who had β2MG levels <2.5xa0mg/L (nxa0=xa049; 4-year PFS rate, 87xa0%; 4-year OS rate, 98xa0%; Pxa0<xa00.001). In multivariate analysis, only a serum β2MG level ≥2.5 mg/L was a significant adverse prognostic factor in regard to PFS (Pxa0=xa00.04; relative risk 3.57). However, it was not significant prognostic factor for OS (Pxa0=xa00.16) in the multivariate analysis. The serum β2MG level at diagnosis is a useful prognostic marker in patients with HL.

Hyper-recovery of platelets after induction therapy is a predictor of relapse-free survival in acute myeloid leukemia.

Abstract We verified the association between standard clinical and laboratory variables and the risk of relapse in acute myeloid leukemia (AML), which led us to retrospectively examine the effect of regeneration of hematopoiesis in patients with newly diagnosed AML. We used data from 230 patients who obtained remission after cytarabine-based induction chemotherapy. Platelet counts ≥500u2009×u2009109/L and hemoglobin levels ≥9u2009g/dL on day 28 after treatment initiation were significantly associated with relapse-free survival (RFS) rate, conferring respective multivariate risk ratios of 0.38 (95% CI: 0.18–0.79) and 0.60 (95% CI: 0.40–0.89) for the occurrence of relapse or death. No disease relapse occurred in core binding factor leukemia patients whose platelet counts recovered ≥500u2009×u2009109/L at 28 days after therapy initiation. We conclude that regeneration of hematopoiesis, especially platelet hyper-recovery, after induction chemotherapy is a significant predictor of RFS in patients with AML.

Intestinal amoebiasis in a patient with acute graft‐versus‐host disease after allogeneic bone marrow transplantation successfully treated by metronidazole

Amoebiasis has rarely been reported in patients undergoing hematopoietic stem cell transplantation, although it is a world‐wide infection and extremely common. We present a case of intestinal amoebiasis unexpectedly revealed by colonoscopy after allogeneic bone marrow transplantation from a human leukocyte antigen‐mismatched unrelated donor for acute myeloid leukemia arising from chronic myelomonocytic leukemia and successfully treated by metronidazole.

R-CHOP therapy alone for limited-stage follicular lymphoma

Irradiation therapy alone is a standard strategy for limited-stage FL, leading to a 10-year progression-free survival (PFS) rate of 30-50%. However, we have been administering R-CHOP therapy alone to patients with limited-stage FL. A total of 35 patients with newly diagnosed FL received R-CHOP therapy with curative intent between 2002 and 2009. The median age of the 35 patients was 61 years; 7 patients had in CS 1 FL, and 28 patients, CS 2 FL. The median number of R-CHOP cycles was 6. On completion of the R-CHOP therapy, 33 patients achieved complete response and 1 showed partial response (PR). The patient showing PR after the completion of R-CHOP was administered additional irradiation. The remaining 1 patient was not evaluated because of discontinuation of hospital visit. In all the 35 patients, the 5-year PFS rate was 70%, and the 5-year overall survival rate was 92%. In the 15 patients with a PFS>5 years, only 1 patient showed disease progression. The outcome of R-CHOP therapy alone in patients with limited-stage FL was at least equivalent to the reported outcome of irradiation therapy alone. R-CHOP therapy could be an alternative to irradiation therapy in limited-stage FL patients.

Successful pregnancy and delivery via in vitro fertilization with cryopreserved and thawed embryo transfer in an acute myeloid leukemia patient after allogeneic bone marrow transplantation

As the number of young long-term survivors of hematopoietic stem cell transplantation (HSCT) for acute leukemia continues to increase, post-transplant infertility is becoming a significant concern. HSCT, particularly with cyclophosphamide and total body irradiation conditioning, is known to cause secondary premature ovarian failure, resulting in infertility. To preserve post-transplant fertility, several methods have been proposed, including in vitro fertilization (IVF) with embryo cryopreservation. Due to the aggressiveness of acute leukemia, however, patients have little chance to undergo egg harvesting and IVF before they must begin receiving chemotherapy. To the best of our knowledge, there have been no detailed reports of successful pregnancy after HSCT using IVF with embryo cryopreservation and transfer in a patient with acute myeloid leukemia. Here, we report the case of a 42-year-old woman with acute myeloid leukemia who became pregnant 2xa0years and 2xa0months after allogeneic bone marrow transplantation via IVF-embryo transfer with an egg collected after induction therapy and delivered a full-term healthy infant.

Outcome and prognostic factors among patients who underwent a second transplantation for disease relapse post the first allogeneic cell transplantation

Abstract The prognosis for disease relapse after first hematopoietic cell transplantation (HCT1) is poor. Here, we present a retrospective multicenter study to evaluate the clinical outcome and the prognostic factors for second hematopoietic cell transplantation (HCT2). The cohort in this study comprised 60 patients diagnosed with acute leukemia, who underwent HCT2 due to hematological relapse after HCT1. The overall survival (OS) at two years, non-relapse mortality (NRM), and relapse mortality (RM) were 30.3%, 40.9%, and 28.8%, respectively. Multivariate analysis for OS identified the use of a donor other than matched-related (MR) donor (hazard ratios [HR]u2009=u20094.10, 95% confidence intervals [CI]: 1.72–9.74, pu2009=u2009.001) and high disease status (HRu2009=u20092.90, 95% CI: 1.28–6.56, pu2009=u2009.011) as the adverse risk factors for HCT2. On analyzing the combination of factors during HCT1 and HCT2, MR donor, reduced intensity conditioning regimen, and standard status were found to be significant as favorable prognostic factors for OS. Therefore, evaluating these prognostic factors would be helpful in taking decisions regarding post-relapse management.