Yoko Shimohakamada

Varicella-zoster virus infection in adult patients after unrelated cord blood transplantation: a single institute experience in Japan

Summary. Varicella‐zoster virus (VZV) infection was studied in 40 adult patients who underwent cord blood transplantation (CBT) from unrelated donors. Twenty‐five patients developed VZV reactivation at a median of 5 months after CBT (range 1·7–26 months). The cumulative incidence of VZV reactivation after CBT was 80% at 30 months. Twenty‐two patients developed localized herpes zoster. The remaining three patients developed atypical non‐localized herpes zoster, which was associated with visceral dissemination in one patient. All the patients responded well to antiviral therapy. Unexpectedly, the absence of grade II–IV acute graft‐versus‐host disease (GVHD) was associated with a higher rate of VZV reactivation after CBT (100% versus 55%, P = 0·01). These results suggest that recovery of VZV‐specific immune responses after CBT is delayed even in patients without severe acute GVHD.

Remission of Acute Myeloblastic Leukemia After Severe Pneumonia Treated With High-Dose Methylprednisolone

We report a case of acute myeloblastic leukemia (AML)-M2 (by French-American-British classification) with t(8;21) (q22;q22) that was complicated with severe pneumonia. The patient tested positive by fluorescence in situ hybridization (FISH) for AML1 splitting and positive by reverse transcriptase polymerase chain reaction (RT-PCR) for chimeric AML1/ MTG8 messenger RNA (mRNA), which indicated splitting of the MTG8 gene on chromosome 8 (q22) and the AML1 gene on chromosome 22 (q22). High-dose methylprednisolone was administered, and the leukemic cells disappeared without chemotherapy, although dysplastic hematopoietic cells were observed transiently after the first therapy. After the disappearance of leukemic cells, FISH for AML1 splitting was negative, and real-time PCR results for quantitative chimeric AML1/ MTG8 mRNA were less than the detectable level, however, RT-PCR results for AML1/MTG8 mRNA remained positive. These findings suggest that the patient acquired morphological, cytogenetic, and possibly molecular genetic remission by the synergistic effects of severe infection and high-dose methylprednisolone.

Unrelated cord blood transplantation for a human immunodeficiency virus-1-seropositive patient with acute lymphoblastic leukemia

Unrelated cord blood transplantation for a human immunodeficiency virus-1-seropositive patient with acute lymphoblastic leukemia

Instruction of naive CD4+ T‐cell fate to T‐bet expression and T helper 1 development: roles of T‐cell receptor‐mediated signals

Using T‐cell receptor (TCR) transgenic mice, we demonstrate that TCR stimulation of naive CD4+ T cells induces transient T‐bet expression, interleukin (IL)‐12 receptor β2 up‐regulation, and GATA‐3 down‐regulation, which leads to T helper (Th)1 differentiation even when the cells are stimulated with peptide‐loaded I‐Ab‐transfected Chinese hamster ovary cells in the absence of interferon‐γ (IFN‐γ) and IL‐12. Sustained IFN‐γ and IL‐12 stimulation augments naive T‐cell differentiation into Th1 cells. Intriguingly, a significant Th1 response is observed even when T‐bet–/– naive CD4+ T cells are stimulated through TCR in the absence of IFN‐γ or IL‐12. Stimulation of naive CD4+ T cells in the absence of IFN‐γ or IL‐12 with altered peptide ligand, whose avidity to the TCR is lower than that of original peptide, fails to up‐regulate transient T‐bet expression, sustains GATA‐3 expression, and induces differentiation into Th2 cells. These results support the notion that direct interaction between TCR and peptide‐loaded antigen‐presenting cells, even in the absence of T‐bet expression and costimulatory signals, primarily determine the fate of naive CD4+ T cells to Th1 cells.

Herpes simplex virus infection in adult patients after unrelated cord blood transplantation: a single-institute experience in Japan

Summary:Herpes simplex virus (HSV) infection in adult patients who underwent cord blood transplantation (CBT) from unrelated donors was studied. None of nine HSV-seronegative patients developed HSV disease after CBT. Of 28 HSV-seropositive patients, seven (25%) developed HSV disease at a median of 92 days after CBT (range, 52–239 days). The cumulative incidence of HSV disease in HSV-seropositive patients was 27% at 12 months after CBT. The manifestations of HSV disease included gingivostomatitis (three patients), herpes labialis (two patients), localized herpes facialis of the nose (one patient), and disseminated eczema herpeticum (one patient). HSV disease recurred in two patients as gingivostomatitis and disseminated eczema herpeticum. All the patients responded to antiviral therapy. The presence of grade II–IV acute graft-versus-host disease (GVHD) was significantly associated with a higher rate of HSV disease after CBT (51 vs 8%, P=0.015). These results suggest that the recovery of HSV-specific immune responses is delayed in patients who develop grade II–IV acute GVHD after CBT.

Unrelated Cord Blood Transplantation with a Reduced-Intensity Conditioning Regimen following Autologous Transplantation for Multiple Myeloma

Two patients, 51- and 45-year-old men with stage III immunoglobulin G multiple myeloma, achieved partial and complete remissions, respectively, after conventional chemotherapy. They both received high-dose melphalan (200 mg/m2) with autologous stem cell transplantation (ASCT). Eighty-four and 78 days after ASCT, the patients underwent unrelated cord blood transplantation (CBT) following treatment with total-body irradiation (2 Gy), fludarabine (90 mg/m2), and melphalan (140 mg/m2). Neutrophil engraftment was attained on day +27 in patient 1 and day +15 in patient 2. Full donor chimerism of the marrow cells was confirmed. Regimen-related toxicity in both patients remained within grade I. Grades I and II acute graft-versus-host disease (GVHD) occurred in patients 1 and 2, respectively, but improved without steroid therapy. Both patients developed limited chronic GVHD of the skin but needed no treatment. The serum paraprotein level in patient 1 decreased further after ASCT and CBT but remained at minimally detectable levels. The serum and urine paraprotein levels in patient 2 remained below detectable limits. These results suggested that CBT with a reduced-intensity conditioning regimen after high-dose chemotherapy with ASCT is a new promising approach for the treatment of multiple myeloma.

Therapy-Related Myelodysplastic Syndrome in a Case of Cutaneous Adult T-Cell Lymphoma

We report a case of therapy-related myelodysplastic syndrome (t-MDS) in adult T-cell lymphoma. A 69-year-old man suffered from cutaneous adult T-cell lymphoma, which was treated with radiation to the skin and combination chemotherapy of CHOP-V-MMV and VEPA-B.After 14 months of these therapies, anemia and thrombocytopenia appeared, and bone marrow aspiration smears showed immature myeloblasts, dysplastic erythroblasts, and micromegakaryocytes. Therapy-related MDS of refractory anemia with an excess of blasts was diagnosed. Cytogenetic study of the bone marrow cells showed 5q— and additional abnormalities. Rearrangement of the MLL gene was observed in the bone marrow cells. Mutations of N-ras codons at 12, 13, and 61, p53 tumor suppressor gene, and monoclonal integration of human T-lymphotrophic virus —1 provirus DNA were not observed in the bone marrow cells.The patient died of pneumonia 21 months after diagnosis of cutaneous adult T-cell lym-phoma.