Enlightenment and lesson from the successful treatment of acute superior mesenteric artery embolism.

 Despite recent advances, treatment of acute superior mesenteric artery embolism (SMAE) in emergency is still very difficult. The comparative rarity, the difficulty of early diagnosis, and the extremely high mortality of SMAE give us the sufficient reasons to report our successful experience in curing a patient with acute SMAE. In the present case, the patient was diagnosed early without evidence of intestinal necrosis. The diagnosis of SMAE was verified by computed tomography angiography (CTA). A comprehensive treatment was immediately employed including a combination of intra-arterial thrombolysis and embolectomy operation with emergent laparotomy. We summarize that the successful treatment of superior mesenteric artery embolism depends on early diagnosis and timely reestablishment of arterial flow under the support of general treatments such as prevention of sepsis and control of organic insufficiencies. Through a combined treatment, patient's life could be saved without complications.

Successful treatment of pure red cell aplasia with repeated, low doses of rituximab in two patients after ABO-incompatible allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.

We describe two patients with acute myeloid leukemia successfully treated with anti-CD20 antibody for pure red cell aplasia (PRCA) following ABO-mismatched allogeneic hematopoietic stem cell transplantation (HSCT). PRCA following HSCT is associated with major ABO incompatibility between donor and recipient and is due to an inhibition of donor erythroid precursors by residual host isoagglutinins. The first patient developed PRCA resistant to several treatment options including donor-derived leukocyte infusions (DLI), high-dose erythropoietin (EPO), and rapid tapering of cyclosporin A (CsA). This patient also received anti-viral therapy as CMV and parvovirus B19 infections were regarded as additional causes of PRCA. Due to a loss of donor chimerism, he underwent second HSCT, but PRCA still persisted. He showed no evidence of graft-versus-host disease (GVHD). Finally he was administered anti-CD20 antibody (rituximab) at a dose of 150/m2 and PRCA resolved in a short period of time. The case was complicated by life-threatening pulmonary aspergillosis with septic shock, successfully treated with anti-fungal therapy. The second case concerns a patient, who revealed PRCA after major ABO-incompatible HSCT from his brother. Considering our experience with the previously described patient, he proceeded to rituximab at a dose of 150/m2 as first line treatment. We observed rapid recovery from PRCA without any side effects. We conclude that rituximab seems to be a promising therapeutic option in patients with PRCA after ABO-mismatched HSCT, in whom conventional treatment fails.

Radiation nephritis following total-body irradiation and cyclophosphamide in preparation for bone marrow transplantation.

Two children prepared for bone marrow transplantation with total-body irradiation and cyclophosphamide developed hypertension, microscopic hematuria, proteinuria, diminished renal function, and anemia six months after transplantation. Light microscopy of the kidneys revealed mesangial expansion, glomerular capillary wall thickening, and lumenal thrombosis. Electron microscopy demonstrated widening of the subendothelial space due to the deposition of amorphous fluffy material. In one patient, immunofluorescence microscopy revealed glomerular capillary wall deposition of fibrin and immunoglobulins. The clinical and histologic findings support the diagnosis of radiation nephritis. Patients prepared for bone marrow transplantation with total-body irradiation and cyclophosphamide should be followed closely after transplantation for the development of hypertension, proteinuria, and renal insufficiency.

Autologous bone marrow transplantation in secondary acute monoblastic leukemia following Hodgkin's disease.

Acute non lymphocytic leukemia (AnLL) is the most common second malignancy (SM) in survivors of childhood Hodgkin's Disease (HD). Chemotherapy responsiveness is usually poor and death ensues briefly after diagnosis. We report the case of a 13 year-old girl, affected by HD, stage IV, mixed cellularity, who developed AnLL one year after the HD treatment was stopped. Autologous Bone Marrow Transplantation (ABMT) was performed 9 months after complete remission (CR) was achieved by chemotherapy. Presently, the patient is alive and on continues CR, 3 years and 7 months after ABMT. ABMT may be a promising approach for secondary AnLL, the prognosis of which is almost invariably fatal with conventional chemotherapy.

Elevated post-stimulatory intracellular adenosine 3,5-cyclic monophosphate (cAMP) levels are found in peripheral blood cells after ABMT.

Intracellular cyclic adenosine monophosphate (cAMP) levels were measured in the peripheral mononuclear cells of 25 recipients of ABMT after stimulation with forskolin (10(-4) M), cholera toxin (1 microgram/ml) and prostaglandin E2 (PGE2, 10(-6) M). Significantly increased post-stimulatory cAMP levels were found in cells derived from patients' cells less than 30 days after ABMT (after forskolin stimulation: mean 89.7 +/- 45.4 pmol per 5 x 10(6) cells, p < 0.001; after cholera toxin stimulation: mean 78.6 +/- 37.9 pmol per 5 x 10(6) cells, p = 0.003; after PGE2 stimulation: mean 93.6 +/- 36.6 pmol per 5 x 10(6) cells, p < 0.001). However, at a later time after ABMT (7-60 months), cAMP levels had returned to normal and no significant differences in intracellular cAMP content between cells from patients and normal individuals could be detected. In addition, in six patients cAMP levels after PGE2 stimulation were measured serially pre- or peri-transplantation up to a time when haematologic recovery had occurred: the significantly elevated inducible cAMP levels found early post-ABMT returned to normal with peripheral blood reconstitution. This observation could be of interest in the post-transplantation period, because cAMP, as a 'second messenger', is a modulator of the immune system.

Donor leucocyte infusions after chemotherapy for patients relapsing with acute leukaemia following allogeneic BMT.

Four patients with acute myeloid leukaemia relapsed within 6 months of allogeneic BMT. Three patients were treated with cytosine arabinoside and amsacrine while the fourth received no chemotherapy. All patients received infusions of leucocytes obtained by repeated leukapheresis from the original bone marrow donor. Three patients developed GVHD requiring immunosuppressive therapy. One of these achieved a complete remission which has been sustained for more than 1 year with 100% donor haematopoiesis. The other patients died with persistent leukaemia 45-134 days after the infusions of donor cells. We conclude that the addition of marrow donor leucocytes to salvage chemotherapy may produce durable remissions in patients with acute myeloid leukaemia relapsing after BMT and that this may be due to a graft-versus-leukaemia effect.

Cutaneous monoblastic leukemia as a first sign of relapse six years after autologous bone marrow transplantation for acute leukemia.

A patient with acute monoblastic leukemia (AML, M5A) was treated successfully in December 1987. In 1993 after 6 years in complete remission, she presented with an intracutaneous nodular mass on her right upper arm which was resected in toto and shown to be undifferentiated monoblastic leukemia. Two further chloroma lesions were excised in July 1994 and March 1995 respectively. Bone marrow cytology and histology always showed a continuing complete remission with no evidence of leukemia relapse. In July 1995 she presented with a disseminated skin infiltrate and a relapse with 80% monoblasts in the bone marrow. After one course of chemotherapy (Idarubicin/Ara-C), a second complete remission was achieved and her leukemic skin infiltrate disappeared completely. This case illustrates that chloromas of the skin can occur as late as 6 years after treatment for AML and also emphasizes that the occurrence of a chloroma does not necessarily mean immediate leukemia relapse. It also stresses that a second complete remission can be achieved with standard AML-induction therapy despite widespread leukemic skin infiltrates in such patients.

[Autologous bone marrow transplantation in acute myeloid leukemias: a report of 7 cases].

Seven patients with acute myeloid leukemias (AML) in complete remission (CR) were treated with high dose chemotherapy and/or total body irradiation (TBI) followed by autologous bone marrow transplantation (ABMT). The clinical status of the 7 cases at ABMT were as follows: 5 in CR1 (2 with standard risks and 3 with high risks) and 2 in CR2 (both with standard risks). The conditioning regimens used for ABMT were cyclophosphamide plus TBI in 3 cases, high dose busulfan plus cyclophosphamide in 3 cases, and BACT program chemotherapy in 1 case. All 7 cases showed hemopoietic reconstitution after ABMT; no death occurred within the post-transplantation aplasia period, but hepatotoxicity was observed with high dose busulfan. Up to December, 1989, 2 patients in CR1 with standard risk receiving transplants had survived, disease free, for 26 and 18 months, respectively; one of 2 patients in CR2 with standard risk receiving transplants had survived for 30 months, and the other died at the 9th month after ABMT with no sign of leukemia relapse. Two of the 3 patients with high risk relapsed at 5 months post-ABMT and the third was in continuous CR for 5.5 months.

[Pulmonary disease as the chief manifestation of chronic graft-versus-host disease after allogeneic bone marrow transplantation].

A 17-year-old man diagnosed as acute myelogenous leukemia (M5a) underwent allogeneic bone marrow transplantation from his HLA-identical, MLC non-reactive sister on the occasion of the second complete remission. On day 14 engraftment was confirmed by karyotypic expression. The patient had no evidence of acute graft-versus-host disease (GVHD), therefore cyclosporine A was discontinued on day 62. Having complained of cough and dyspnea by day 100, the patient was diagnosed as interstitial pneumonitis (IP) based on chest X-ray findings. However, no other typical signs of chronic GVHD were present except for modest abnormality of liver function. Since there was no evidence of infection on bronchofiberoscopic examination and prednisolone was very effective, it was considered that the IP might be pulmonary disease of chronic GVHD. It has been reported that HLA-DR which is not normally found, is expressed on epithelial tissues of the patient with GVHD. In this case alveolar epithelial cells were positive for LN-3 (anti-HLA-DR). In conclusion, pulmonary disease in this case may represent a possible manifestation of chronic GVHD, thus suggesting that the current case could provide information to ascertain the mechanism of chronic GVHD.

[Analysis of clinical outcomes of 63 children with acute monocytic leukemia].

OBJECTIVE: To evaluate the outcomes of childhood acute monocytic leukemia (AML-M5) and explore the indications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for children with AML-M5. METHOD: Seventy-five AML-M5 patients and 201 non-AML-M5 AML patients were enrolled in this retrospective analysis. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method and prognostic factors were evaluated by COX regression with SPSS. RESULT: (1) Twelve patients gave up treatment after confirmed diagnosis. Two patients died on the second day after chemotherapy. Of the 61 patients, 73.8% (45/61) achieved complete remission (CR) after two courses of chemotherapy. The 5-year EFS rate was 34.5% ± 6.8%. But of the 117 non-AML-M5/M3 AML patients, the 5-year EFS rate was 51.0% ± 4.9%. (2) Multivariate analysis showed that age ≥ 10 y, the proportion of bone marrow blast cell counts ≥ 15% after the first induction therapy, not CR after two courses of chemotherapy were risk factors for the long-term prognosis. (3) Of the 20 patients whose bone marrow blast cell counts ≥ 15% after the first induction therapy, 5 patients who choose allo-HSCT had a better OS than the other 15 patients who choose chemotherapy only (60.0% ± 21.9% vs. 7.3% ± 7.1%, P = 0.024). CONCLUSION: Children with AML-M5 had a poorer prognosis than the other AML patients; patients whose bone marrow blast cell counts ≥ 15% after the first induction therapy chose allo-HSCT had a better prognosis. At present, there is no enough evidence to support that patients whose bone marrow blast cell counts < 15% after the first induction therapy should choose unrelated donor for allo-HSCT.

Secondary biliary cirrhosis as a consequence of graft-versus-host disease.

A 9-yr-old white girl with acute monoblastic leukemia received an HLA-identical, mixed lymphocyte culture-nonreactive bone marrow transplant from her sister. Twelve days after the transplant, a diffuse, pruritic, maculopapular rash involving the entire body surface (including the palms and soles) developed. Subsequent skin biopsy was consistent with cutaneous graft-versus-host disease, and biopsy-proven hepatic involvement manifested by severe, unremitting cholestatic jaundice soon followed. The patient's biliary status as monitored by serial liver biopsies demonstrated progression from chronic graft-versus-host disease to cirrhosis, culminating in death secondary to liver failure 25 mo after transplant.

Graft-versus-tumour effect in non-small-cell lung cancer after allogeneic peripheral blood stem cell transplantation.

Clinical evidence of a graft-vs.-tumour effect in solid tumours after haematopoietic stem cell transplantation is lacking. We report for the first time a complete and durable regression of a stage IB non-small-cell lung carcinoma in a patient who had received an allogeneic peripheral blood haematopoietic stem cell transplant for acute myeloblastic leukaemia in first complete remission. Disappearance of the tumour coincided with development of graft-vs. -host disease. This suggests that simultaneous generation of cytotoxic T lymphocytes against lung carcinoma cells could have been responsible for the regression. This unique clinical observation broadens the possibility of using allogeneic haematopoietic stem cell transplantation in treating neoplasias lacking significant sensitivity to chemotherapy.

Effective treatment of thymic carcinoma with operation and combination chemotherapy against acute monocyte leukemia: case report and review of the literature.

Thymic carcinoma associated with acute monocyte leukemia (AMoL) and a history of choriocarcinoma was diagnosed in a 58-year-old female. We found no other such case in a literature search. She was first treated with DCMP therapy: daunorubicin, cytosine arabinoside, 6MP-riboside, and prednisolone against AMoL. After induction chemotherapy, complete AMoL remission was attained. Chest CT scan after chemotherapy revealed regression of the mediastinal tumor. Resection of the tumor included the left upper lobe of the lung, phrenic nerve and pericardium. Pathological diagnosis showed poorly or moderately differentiated squamous cell carcinoma. Although the patient died of pneumonia during chemotherapy for relapsed AMoL, chest X-ray and CT revealed no recurrence of the mediastinal tumor after the original operation. Judging from this case and other successful cases of chemotherapy, we feel that intensive chemotherapy may be a beneficial strategy against thymic carcinoma.

Regeneration of CALLA (CD10+), TdT+ and double-positive cells in the bone marrow and blood after autologous bone marrow transplantation.

In this prospective study we investigated the frequency of CD10+, TdT+ and CD10+TdT+ mononuclear cells in the bone marrow (BM) and peripheral blood (PB) before and after autologous bone marrow transplantation (ABMT). 49 patients treated for acute lymphoblastic or myeloblastic leukaemia, malignant lymphoma or multiple myeloma were included. A significant increase in CD10+ cells occurred in BM in both children and adults after ABMT. In children, we also found a significant increase in CD10+ cells in PB. In individual patients remaining in remission, up to 34% CD10+ cells having a normal Ig kappa/lambda light chain ratio were recorded after ABMT. In children, the percentage of TdT+ and CD10+ TdT+ cells increased significantly in BM. In most cases the CD10/TdT-ratio was greater than 1.0, but during early regeneration after ABMT this ratio was less than 1.0 in several patients remaining in complete remission. In patients remaining in remission, CD10+TdT+ cells were detected in the blood in only 2 out of 140 samples tested, and the proportion of these cells never exceeded 0.03%. We conclude that quantitation of CD10+TdT+ cells in peripheral blood is helpful in the evaluation of complete remission in patients treated for pre-B-ALL.

Intracerebral chloroma complicating acute monocytic leukemia.

We present the case of a 21-year-old woman with an acute monocytic leukemia. When she was in complete hematological remission, she developed rapid progressive hemiparesis on the right caused by a left frontoparietal chloroma as confirmed by surgery and histological examination. Postoperatively, the patient recovered completely, and x-ray therapy followed. Since intracerebral myeloblastic tumors are extremely rare and since the neurosurgeon may be involved in treatment of these lesions, we are encouraged to present our findings.

Fatal B-cell lymphoproliferative syndrome in allogeneic marrow graft recipients. A clinical, immunobiological and pathological study.

We have studied four cases of fatal B-cell lymphoproliferative syndrome (LPS) developing among 333 patients (incidence 1.2%) treated with allogeneic bone marrow transplantation (BMT). All four patients had received a T-cell depleted graft. Onset of the first clinical symptoms (palpable lymph node enlargement in three and IgA-lambda paraproteinemia in two patients) occurred between 41 and 188 days post-BMT (median 76 days). The course of the LPS was rapidly progressive in all cases, leading to death in 2-5 weeks. The peripheral blood showed progressive pancytopenia with disproportionally high numbers of activated NK cells, apparently compensating for the T-cell deficiency. Post-mortem histological studies disclosed polymorphic B-cell proliferations, most pronounced in the lymph nodes, spleen, liver, lungs and kidneys. Lymphohemopoietic cells were of donor origin in three patients. In the fourth patient, graft failure suggested a host origin for the proliferating cells. Immunophenotyping and gene rearrangement analysis revealed polyclonal proliferation in one patient, monoclonal proliferation in another patient, and an oligoclonal pattern in the other two patients. The clinical behavior of the LPS was independent of clonality. Immunohistologically, the proliferating cells showed characteristics of relatively mature B-cells in three cases, and pre-B-cell features in one case. Epstein Barr virus (EBV) serology indicated seroconversion (primary infection) in one child, and chronic active EBV infection in both adults. EBV DNA as well as EBV nuclear antigen (EBNA) were detected in infiltrated tissues of all four patients. The labeling pattern on in situ hybridization suggested a replicative EBV infection comparable to that in lymphoblastoid cell lines. We conclude that EBV-associated LPS developing as a result of post-transplant immunodeficiency is a distinct clinicopathologic entity, differing from non-Hodgkin's lymphoma (including Burkitt's lymphoma) and infectious mononucleosis of the immunocompetent host.