Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip.

Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition.

Living-donor lobar lung transplantation for broncho-bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation: does bronchiolitis obliterans recur in transplanted lungs?

We report a successful case of living-donor lobar lung transplantation (LDLLT) for therapy-resistant broncho-bronchiolitis obliterans (BBO) after allogeneic hematopoietic stem cell transplantation (HSCT). Bronchiolitis obliterans (BO) is one of the late-onset noninfectious pulmonary complications that occur after allogeneic HSCT and is usually resistant to immunosuppressive therapy. A 17-year-old girl with acute lymphoblastic leukemia (ALL) had undergone allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling in 1997. Five years later, she relapsed with ALL and was treated with chemotherapy following stem cell rescue and donor lymphocyte infusion from the original BMT donor. Eight months later, BBO resistant to immunosuppressive therapies, including rituximab, developed in combination with chronic graft-versus-host disease (GVHD). In February 2004, the patient underwent LDLLT from 2 other family members who were mismatched at 3 HLA loci. The patient has been in good health for more than 30 months following LDLLT and shows no sign of BBO in the transplanted lungs, just as with other patients who have undergone lung transplantation for BO associated with chronic GVHD. LDLLT may therefore be considered a viable therapeutic option for the treatment of BO after allogeneic HSCT.

Macrophage colony-stimulating factor enhances rituximab-dependent cellular cytotoxicity by monocytes.

Recent studies suggest that monocytes are the dominant effectors by which rituximab induces cell death in B-cell lymphoma. Because macrophage colony-stimulating factor (M-CSF) can enhance the cytotoxicity of monocytes, the authors examined whether this growth factor can enhance their ability to kill lymphoma cells in vitro. Monocytes derived from a healthy volunteer were cultured for 48 h in the presence or absence of M-CSF. Monocytes stimul ated with M-CSF were significantly more cytotoxic to Daudi B-cell lymphomas than unstimulated monocytes. Flow cytometry revealed that M-CSF increased monocyte expression of Fcgamma receptors III and I by 1.6- and 1.5-fold, whereas the expression of Fcgamma receptor II remained unchanged. These results suggest that pretreatment with M-CSF can improve the therapeutic efficacy of rituximab against intractable CD20(+) lymphoma.

Successful treatment of minimal residual disease-positive Philadelphia chromosome-positive acute lymphoblastic leukemia with imatinib followed by reduced-intensity unrelated cord blood transplantation after allogeneic peripheral blood stem cell transplantation.

We describe a 35-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who received allogeneic sibling donor peripheral blood stem cell transplantation (PBSCT) and entered a second complete remission. Upon detection of BCR-ABL transcripts after PBSCT, the patient received imatinib, leading to molecular remission. Following the failure of donor leukocyte infusions, she underwent reduced-intensity unrelated cord blood transplantation (RI-UCBT), and has continued durable molecular remission for more than 30 months without substantial graft-versus-host disease. Because of a lack of adverse effects of imatinib on transplantation outcome, a treatment strategy consisting of molecular monitoring-guided initiation of imatinib followed by RI-UCBT may be promising in the management of Ph+ ALL after allogeneic SCT.

Complete and durable remission of refractory mantle cell lymphoma with repeated rituximab monotherapy.

We encountered a 53-year-old man with general fatigue. Bone marrow investigations revealed an infiltration of CD20+CD5+CD23- cells and the presence of cyclin D1 lymphoid cells, leading to a diagnosis of mantle cell lymphoma, clinical stage IV. The first 2 lines of chemotherapy, CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, and prednisolone) and fludarabine-cyclophosphamide, produced only a transient decrease in serum lactic dehydrogenase levels, without a clinical remission. Because of the persistence of bone marrow hypoplasia, monotherapy with 375 mg/m2 rituximab was administered. The pancytopenia gradually improved, and a complete remission was obtained after 4 cycles of rituximab. The patient remains in complete remission 21 months after the third rituximab therapy for maintenance.

Prospective trial of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for relapsed leukemia after allogeneic stem cell transplantation.

To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.