[A Case of Adult T-Cell Leukemia/Lymphoma with Severe Hand-Foot Syndrome during Administration of Modified LSG15 Regimen].

The patient was a 56-year-old woman. A modified LSG15(VCAP-AMP-VECP)regimen was initiated as the first-line treatment for acute adult T-cell leukemia/lymphoma. On day 13 from the initiation of the second course of chemotherapy, the onset of hand-foot syndrome(HFS)(hands: Grade 2; feet: Grade 1)occurred. Therefore, the administration of a heparin analog cream and betamethasone butyrate propionate ointment was initiated. On day 20 from the start of the second course of chemotherapy, the foot symptoms improved; however, hand symptoms deteriorated to Grade 3. Frequent use of alcohol-based hand hygiene products is associated with infection prevention during neutropenia, but was likely an exacerbating factor. The symptoms gradually improved after this was taken into consideration, and the usage was discontinued. At the start of the third course, the symptoms had improved to Grade 1, and chemotherapy was continued. On day 11, symptoms worsened(Grade 2). HFS management was performed similar to that in the second course, and symptoms improved again.

[Successful treatment with L-asparaginase-based combination chemotherapy for refractory T-cell post-transplant lymphoproliferative disorder].

A 31-year-old man underwent kidney transplantation in 1996, and had been on immunosuppressants. In 2005, he presented with discomfort on swallowing. Swelling of the left tonsil and a mediastinal mass were observed. A biopsy of the left tonsil showed a monotonous proliferation of atypical lymphocytes suggesting post-transplant lymphoproliferative disorder (PTLD). The reduction of immunosuppressants did not result in any clinical improvements, and he developed bilateral cervical lymphadenopathy. A biopsy of the cervical lymph node also showed monotonous proliferation of TdT, CD3, CD5, CD7, CD10, and CD34-positive immature cells. T-cell receptor rearrangement, but not EBER, was detected. Based on these findings, monomorphic T-cell PTLD was diagnosed. He was treated with four different chemotherapeutic regimens without any clinical improvements, and the PTLD became leukemic. Chemotherapy consisting of L-asparaginase, vincristine, and dexamethasone (LVD) was then given, which resulted in massive tumor lysis. However, after two courses of LVD, complete remission was achieved. T-cell PTLD is a rare disorder, characterized by its refractoriness to chemotherapy as opposed to B-cell PTLD. Our experience suggests that L-asparaginase-based chemotherapy may improve the prognosis of T-cell PTLD.

Zerumbone, a bioactive sesquiterpene, induces G2/M cell cycle arrest and apoptosis in leukemia cells via a Fas- and mitochondria-mediated pathway.

We demonstrated here for the first time that zerumbone (ZER), a natural cyclic sesquiterpene, significantly suppressed the proliferation of promyelocytic leukemia NB4 cells among several leukemia cell lines, but not human umbilical vein endothelial cells (HUVECs), by inducing G2/M cell cycle arrest followed by apoptosis with 10 microM of IC50. Treatment of NB4 cells with growth-suppressive concentrations of ZER resulted in G2/M cell cycle arrest that was associated with a decline of Cyclin B1 protein, but with the phosphorylation of ATM/ Chk1/Chk2. In addition, ZER induced the phosphorylation of Cdc25C at the Thr48 residue and Cdc2 at the Thr14/Tyr15 residues. Furthermore, ZER-induced apoptosis in NB4 cells was initiated by the expression of Fas (CD95)/Fas Ligand (CD95L), concomitant with the activation of caspase-8. ZER was also found to induce the cleavage of Bid, a mediator that is known to connect the Fas/CD95 cell death receptor to the mitochondrial apoptosis pathway. ZER also induced the cleavage of Bax and Mcl-1 proteins, but not Bcl-2 or Bcl-XL. ZER-induced apoptosis took place in association with a loss of the mitochondrial transmembrane potential as well as the activation of caspase-3 and -9, resulting in the degradation of the proteolytic poly (ADP-ribose) polymerase (PARP). ZER also triggered a release of cytochrome c into the cytoplasm. Both antagonistic anti-Fas antibody ZB4 and pan-caspase inhibitor Z-VAD inhibited ZER-induced apoptosis in NB4 cells. Taken together, ZER is an inducer of apoptosis in leukemic cells that specifically triggers the Fas/CD95- and mitochondria-mediated apoptotic signaling pathway.

Recurrence of autoimmune disease after autologous peripheral blood stem cell transplantation for multiple myeloma.

There have been a number of reports on the improvement of concomitant autoimmune disease (AID) after autologous hematopoietic stem cell transplantation (SCT) performed for hematologic malignancy. However, in some cases of hematologic malignancy with AID, exacerbation of AID after autologous SCT has been reported. We have treated 27 adults with multiple myeloma with single or tandem autologous SCT. After peripheral blood stem cells were collected and stored without CD34+ cell selection or T-cell depletion, all patients received melphalan (200 mg/m2) as a conditioning regimen. In 2 patients with a history of AID (one with rheumatoid arthritis [RA] and the other with bullous pemphigoid [BP]) and in 1 patient with Sjögren syndrome, AID recurred 7 to 12 months after autologous SCT. The RA and BP were in durable remission before SCT, and no Sjögren syndrome-related disease activity was clinically documented at the time of SCT. No progression of the myeloma was observed when the AIDs recurred. The patients required systemic steroid therapy for their AID, and successful control of the disease was achieved. Our experience suggests that autologous SCT with unmanipulated stem cells for myeloma is unlikely to cure preexisting AID; rather, the AID may worsen. Transplantation physicians should be aware of this possible complication.

[Pulmonary tuberculosis and adenovirus-hemorrhagic cystitis after autologous peripheral blood stem cell transplantation for follicular lymphoma].

A 58-year-old man had a relapsed follicular lymphoma (Grade 2) and was treated with mitoxantrone, fludarabine and dexamethasone followed by rituximab, and achieved partial remission. The patient then underwent high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT). Three days after starting high-dose therapy, he developed a fever, and a chest X-ray revealed pneumonia in the right lower lung. Despite of the administration of antibiotics and the recovery of neutrophils to normal levels, the pneumonia got worse. Bronchoalveolar lavage (BAL) was performed on day 32, the Ziehl-Neelsen staining of the BAL fluid showed acid-fast bacilli, and the culture grew Mycobacterium tuberculosis. The patient was diagnosed as having pulmonary tuberculosis and placed on an antituberculosis regimen (isoniazid, rifampicin, ethambutol, pyrazinamide). On day 43 he also developed hemorrhagic cystitis due to adenovirus type 11, and on day 49 positive CMV antigenemia was detected, which were treated supportively. On day 75 he developed pneumonia probably due to Pneumocystis jirovecii, which was treated with sulfamethoxazole/trimethoprim. The pulmonary tuberculosis resolved completely 4 months after starting the treatment, and the hemorrhagic cystitis and pneumocystis pneumonia resolved 1 month after the diagnosis. He remains in complete remission 2 years after transplantation.

[Acute myeloid leukemia presenting with obstructive jaundice and granulocytic sarcoma of the common bile duct].

A 55-year-old man presented with jaundice and edema of the right leg. Tests of the peripheral blood and bone marrow showed leukocytopenia with 6% blasts and 38.3% of myeloperoxidase-positive blasts, respectively. Computed tomography (CT) scanning disclosed thickening of the common bile duct wall. Granulocytic sarcomas were also found at the left chest wall and the pelvic floor. Endoscopic retrograde cholangiopancreatography confirmed the narrowing of the common bile duct. Biopsy specimens of the common bile duct and pelvic masses revealed myeloblastic infiltration. After placement of a naso-biliary drainage tube, chemotherapy consisting of cytarabine (100 mg/m2/ day for 7 days) and idarubicin (12 mg/m2/ day for 3 days) was commenced. The dose of idarubicin was not modified. No serious complications, including delayed hematopoietic recovery, were observed after chemotherapy, and a complete remission was obtained 35 days later. Jaundice and liver dysfunction also gradually improved. The patient continues to receive consolidation therapy and remains in remission 8 months after the onset of his illness.

[Interstitial pneumonia during treatment with thalidomide in a patient with multiple myeloma].

A 66-year-old man was referred to our hospital for the treatment of refractory multiple myeloma with thalidomide. He had a history of an interstitial pneumonia of unknown etiology two months before admission. Eight days after starting 200 mg/ day of thalidomide, he developed dyspnea and fever, followed by a macropapular rash in the trunk. The dyspnea got worse and a CT scan revealed interstitial pneumonia 16 days after the treatment. He required mechanical ventilatory support. Bronchoalveolar lavage fluid revealed eosinophilia, suggesting a thalidomide-induced interstitial pneumonia. Thalidomide was discontinued and methylprednisolone (1000 mg/d x 3 days) was started, and the pneumonia and rash markedly improved within six days. After that the patient contracted MRSA pneumonia and died of MRSA septicemia.