Serum ferritin level is a prognostic marker in patients with peripheral T-cell lymphoma.

INTRODUCTION: The prognostic value of serum ferritin level in patients with peripheral T-cell lymphoma (PTCL) remains unknown. METHODS: We retrospectively analyzed clinical data from 78 consecutive patients with newly diagnosed PTCL that were treated with anthracycline-containing regimens between 1998 and 2011. RESULTS: The patients consisted of 50 males and 28 females with a median age of 64 years (range, 16-83 years). The subtypes of PTCL were 39 PTCL, not otherwise specified and 39 angioimmunoblastic T-cell lymphoma (AITL). The median observation period for the surviving patients was 50 months. The overall survival (OS) was poorer in patients with serum ferritin level above the upper normal limit (n = 28), compared with patients with serum ferritin level within normal range (n = 50; 4-year OS: 23% vs. 72%; P < 0.001). In the multivariate analysis, poor performance status (P = 0.006) and elevated serum ferritin level (P = 0.018) were independent risk factors for poor OS. CONCLUSION: Serum ferritin level is a useful prognostic marker for PTCL.

Bronchiolitis obliterans organizing pneumonia (BOOP) with suspected liver graft-versus-host disease after allogeneic bone marrow transplantation.

We report on a patient with chronic myelogenous leukemia who developed bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation (BMT). A 19-year-old Japanese male complained of dry cough and dyspnea 7 months after BMT. The chest X-ray and computed tomography revealed patchy infiltrates bilaterally. Lung function test, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of BOOP. The patient also suffered from suspected graft-versus-host disease (GVHD) of the liver, after discontinuation of cyclosporine. Furthermore, prednisolone proved effective against the BOOP and the liver dysfunction. These findings indicate that BOOP is a possible pulmonary manifestation of chronic GVHD, and that immunological mechanisms may have effected the onset of BOOP after BMT in this case.

[Successful treatment of hairy cell leukemia with pentostatin].

A 45-year-old woman was admitted to our hospital in August, 1999. Laboratory data showed a white blood cell count of 5,050/microliter with 78% abnormal lymphocytes, hemoglobin 6.8 g/dl, platelets 4.8 x 10(4)/microliter, and soluble IL-2 receptor 97,600/ml. The abnormal cells were characterized by a hairy appearance under phase contrast microscopy, and showed strong tartrate-resistant acid phosphatase activity. Immunophenotype analysis revealed that these cells were positive for CD11c, CD19 and CD25, and negative for CD5. Bone marrow biopsy showed diffuse proliferation of hairy cells with moderate myelofibrosis. We diagnosed the patient as having European-American-type hairy cell leukemia. Pentostatin was administered at a dose of 5 mg/m2 weekly. After twelve doses, the peripheral blood data returned to the normal range with no hairy cells in the blood or bone marrow, although slight splenomegaly remained. The patient underwent splenectomy in December of the same year, and we were unable to find any hairy cells by histological and immunohistochemical examination. Although most patients with hairy cell leukemia in Japan have the Japanese variant, and the European-American type is rare, pentostatin is as effective as it is for European and American patients.

Severe cardiac toxicity in hematological stem cell transplantation: predictive value of reduced left ventricular ejection fraction.

Eighty patients receiving hematological stem cell transplantation (HCT) with a preparative regimen consisting of total body irradiation (12.5 Gy), cyclophosphamide (4000 or 4500 mg/m2), and thiotepa (400 mg/m2) were evaluated for the development of cardiac toxicity. Patients in whom the pretransplant cumulative dose of anthracycline was more than or equal to 300 mg/m2 showed a lower left ventricular ejection fraction (EF) before HCT compared to patients with less than 300 mg/m2 (0.61 +/- 0.09 vs 0.67 +/- 0.06, P = 0.0010). Patients who had undergone more than or equal to six courses of chemotherapy showed a decreased EF before HCT compared to those after less than six courses (0.67 +/- 0.05 vs 0.63 +/- 0.09, P = 0.03). Three of seven patients (43%) whose pretransplant EF had been less than or equal to 0.55 developed severe cardiac toxicity, characterized by congestive heart failure (CHF) compared with none of 83 patients (0%) whose pretransplant EF had been more than 0.55 (P = 0.00026). Of the three patients who developed severe cardiac toxicity, two were given more than 300 mg/m2 of cumulative anthracycline and underwent 23 courses and six courses of chemotherapy, while the other patient received only two courses of chemotherapy with a total dose of 139 mg/m2 of anthracycline. These results indicate that an increased cumulative dose of anthracycline and number of chemotherapy treatments are correlated with a decrease of the EF and that the EF before HCT is useful for predicting the risk of cardiac complications for recipients who have received chemotherapy.

[Successful emergency operation for subdural hematoma and acute epidural hematoma in a patient with acute promyelocytic leukemia].

A 22-year-old woman was admitted with purpura. Acute promyelocytic leukemia (APL) with disseminated intravascular coagulation (DIC) was diagnosed. On the 17th day after treatment with all-trans retinoic acid (ATRA), left subdural hematoma developed. Although coagulation abnormalities were still observed, emergency surgery was performed. Acute epidural hematoma was confirmed by computed tomographic scan after the operation. A second operation for drainage was successful. Post-operative intracranial hematoma may be caused by rapid decompression induced by surgery, but DIC could also be involved. This case underscored the need for careful consideration of the indications for surgical treatment of such DIC patients, with close follow-up monitoring for the postoperative development of neurological symptoms.

De novo acute myelogenous leukemia with trilineage myelodysplasia associated with t(8;21)(q22;q22).

We describe a rare case of de novo acute myelogenous leukemia with trilineage myelodysplasia (AML/TMDS) associated with t(8;21)(q22;q22). The patient was admitted to our hospital with leukocytopenia. AML/TMDS was diagnosed by excess myeloblasts and morphological findings of bone marrow. The karyotype revealed 45, X, -Y, t(8;21)(q22;q22) in 17 of 20 analyzed mitoses, and also AML1/MTG8 transcripts were detected by the reverse transcription polymerase chain reaction (RT-PCR) method. The patient achieved a complete remission with a combination chemotherapy of daunorubicin, cytarabine, and prednisolone. This case suggests that t(8;21)(q22;q22) may participate in the pathogenesis of AML/TMDS, although this type is usually found as one of the chromosomal abnormalities in de novo acute myelogenous leukemia (AML) with maturation.

Low-dose cytarabine-induced hepatic and renal dysfunction in a patient with myelodysplastic syndrome.

We report a 49-year-old female patient with secondary myelodysplastic syndrome who developed liver dysfunction and acute renal failure caused by low-dose cytosine arabinoside (Ara-C) therapy. Treatment of low-dose Ara-C has widely been used for acute myelogeous leukemia and myelodysplastic syndrome, and it is thought to be a low toxicity except for myelosuppression. The patient complained of a transient adverse reaction in the second and third course of therapy. This rare case indicates that careful observation should be carried out during low-dose Ara-C therapy in view of allergic reactions.

Allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin for treatment of graft failure after allogeneic bone marrow transplantation.

A 43-year-old female with AML-M1 developed late graft failure 4 months after her first allogeneic bone marrow transplant. The patient then underwent a second transplant with peripheral blood progenitor cells obtained from the same HLA-identical brother. The donor peripheral blood progenitor cells were mobilized with granulocyte colony-stimulating factor (10 micrograms/kg daily s.c. for 6 days). The patient received horse anti-thymocyte globulin alone (15 mg/kg per day for 5 days) as the conditioning regimen. Rapid hematopoietic recovery followed a sustained engraftment. The time to reach 0.5 x 10(9)/l neutrophils and 25 x 10(9)/l platelets was 10 and 12 days, respectively. Cytogenetic analysis of bone marrow performed on day +20 demonstrated a 46XY karyotype of donor origin. There was no acute graft-versus-host disease. The patient remains in complete remission with a karnofsky score of 90% 5 months after peripheral blood progenitor cell transplantation. To treat graft failure after allogeneic bone marrow transplantation, allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin alone should be considered as a feasible alternative to marrow transplant.

Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy.

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.

Human parvovirus B19 capsid antigen in granulocytes in parvovirus-B19-induced pancytopenia after bone marrow transplantation.

A patient with refractory anemia with an excess of blasts in transformation developed pancytopenia and a concurrent interstitial pneumonia 110 days after allogeneic bone marrow transplantation. Bone marrow examination showed 0.4% giant proerythroblasts and 86.2% granulocytes, some of them large with a bizarre configuration and the others of normal size. Serum folate level was found low, 0.6 ng/ml. Immunocytochemistry with a B19-specific monoclonal antibody MAB8292 revealed B19 capsid antigen only in erythroblasts and large, bizarre granulocytes, but not in granulocytes of normal size. In situ hybridization of bone marrow cells using digoxigenin-labeled DNA probes detecting parvovirus B19 also demonstrated positive signals in 8.5% of marrow cells. Parvovirus B19 DNA was isolated from the serum and the bronchoalveolar lavage fluid of this patient by the polymerase chain reaction. These findings suggest that neutropenia may be caused by an involvement with parvovirus B19 though a deficiency of folic acid may have in part contributed to the genesis of neutropenia in the patient. The relevance of parvovirus B19 to the interstitial pneumonia remains unclear.

[Complete remission achieved by L-asparaginase, vincristine and prednisolone (LVP) therapy in secondary leukemia (M5a type) with an MLL gene rearrangement].

A 16-year-old boy was operated upon for synovial sarcoma of the right thigh and underwent chemotherapy consisted of adriamycin (320 mg), cisplatin (780 mg), etoposide (4,200 mg) and ifosfamide (30,000 mg). He developed secondary leukemia 18 months after the chemotherapy. Acute lymphoblastic leukemia (L3) was initially diagnosed because of poor staining of alpha-naphtyl butylate esterase and induction chemotherapy with the LVP regimen (L-asparaginase 5,000 U/m2 day 8-21, vincristine 1.5 mg/ m2 day 1, 6, 11, 16, 21, 26, prednisolone 40 mg/m2 day 1-28) was performed. After the therapy was initiated, the leukemia was finally diagnosed as acute momocytic leukemia (M5a) because of the following data; blasts were positive for CD33 and HLA-DR and negative for CD10, CD19 and CD20; serum lysozyme was 104.0 micrograms/ml; re-evaluation revealed that blasts were strongly positive for alpha naphtyl butyrate esterase in a small part of the slides; 95% of the bone marrow cells showed t (9; 11) chromosomal aberration; gene rearrangement was positive for MLL and negative for JH, JK and TCR C beta 1. Nevertheless, complete remission was obtained after 1 course of LVP therapy. He received bone marrow transplantation from an unrelated volunteer donor after 3 courses of consolidation therapy. He has remained in complete remission for 16 months.