Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT.

The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.     

Assessment of split renal function with99mTc-aprotinin

The aim of this work is to correlate the net kidney uptake of^99mTc-aprotinin (TcA) in 103 subjects with separate effective renal plasma flow (ERPF) and some blood chemistry parameters at 90, 180, and 360 min postinjection both in the normal and diseased kidney. Correlations found with separate ERPFs are highly significant at any time (P < 0.001). However, although the slope of the regression line is steeper at 180 min,r tends to deteriorate slightly with time postinjection and a higher intercept on they axis: this pattern is more pronounced if diseased kidneys are considered separately. The following are probably related to the renal handling of TcA: (1) Early scans better reflect blood flow to the kidney, while later scans are more related to the metabolism/excretion tubular mechanisms; (2) correlations found with urea, creatinine, urea clearance, and creatinine clearance are highly significant at any time; (3) in 20 additional patients with diseased kidneys, renal uptake measurements done 360 min postinjection first with TcA and then with DMSA showed better correlations with ERPF employing TcA. Our results indicate that TcA is a feasible indicator of split renal function even at 90 min postinjection when a scan is easily carried out on an outpatient basis.This paper was in part presented at the European Nuclear Medicine Congress, August 14–17, 1984, Helsinki, Finland     

Characterization of spontaneous metastases from autochthonous 3-methylcholanthrene-induced tumors

In mice bearing autochthonous 3-methylcholanthrene-induced tumors metastasis was rare, with only 2 out of 47 (4%) animals showing lung secondaries and 1 showing kidney lesions. Surgical excision of autochthonous growing tumors brought only a slight increase in incidence of metastasis (5 out of 42 mice, 12%). Cell lines were established by in vivo and/or in vitro passage from two kidney metastasis found in the same host (0.13-K1 and 0.13-K3) and from a spontaneous lung metastasis found in 2 mice (mR80/43 and mR80/17) and compared to lines from the respective primary tumors (0.13; R80/17; R80/43). Cell lines from metastases and primary tumors were heterogeneous in tumorigenicity, growth rate, metastatic potential (spontaneous), and colonizing capacity (i.v. inoculation). In particular, the mR80-43 line was more metastatic to lungs upon intravenous injection than the parent R80-43 primary tumor. Similarly the 013-K1 line from a kidney secondary caused more lung nodules when inoculated intravenously than the parent 0.13 line, but this was not the case with the 013-K3 line derived from another kidney secondary in the same host. The R80-17 and mR80-17 lines had similar lung-colonizing capacity. Lung colonizing ability was not strictly correlated to the capacity to form spontaneous metastases. Changes in lung-colonizing capacity occurred in part of the lines (013, 013-K1, R80-17, mR80-17) upon in vitro or in vivo passage. These findings with lines from spontaneous metastases from three autochthonous sarcomas extend previous observations on the heterogenous behavior of transplanted metastatic neoplasms.     

Small-animal PET of tumor angiogenesis using a (76)Br-labeled human recombinant antibody fragment to the ED-B domain of fibronectin.

The aim of this study was to image the extra domain B (ED-B) of fibronectin, an angiogenesis-related target, in solid tumors using small-animal PET. Toward this aim, an ED-B fibronectin-binding human antibody derivative (L19-SIP) was labeled with (76)Br via an enzymatic approach. Biodistribution and imaging studies were performed in human teratoma-bearing mice for up to 48 h after injection. METHODS: L19-SIP was labeled with (76)Br using bromoperoxidase/H(2)O(2). The stability of the labeled antibody was tested both in vitro and in vivo. Biodistribution and small-animal imaging studies (PET and CT) were performed in F9-bearing 129/sv mice (n = 3 or 4). RESULTS: The enzymatic radiobromination approach afforded the labeled antibody in high yield (>55%) under mild reaction conditions. (76)Br-L19-SIP stability in mouse serum proved to be similar to that of the (125)I-labeled analog (>80% of intact material at 48 h after injection). Fast and specific in vivo targeting was obtained in tumors and other organs expressing ED-B fibronectin (i.e., ovaries and uterus). However, slow renal clearance and persistent activity predominately in blood and stomach suggests partial (76)Br-L19-SIP debromination in vivo. This debromination was confirmed in a metabolism study in normal mice. The F9 tumors were clearly imaged by small-animal PET at each considered time point, starting at 5 h up to 48 h after injection. CONCLUSION: (76)Br-L19-SIP specifically accumulated at the target site, enabling detailed small-animal PET of tumor neovasculature. Therefore, targeting the angiogenesis-associated expression of ED-B fibronectin can be a valuable tool for tumor detection using molecular imaging with PET.     

dCTP misincorporation in a Chinese hamster mutator phenotype: the role of GGA genetic context

Clone CSA7 is a CHEF18 hamster cell line that shows an increasedintracellular accumulation of dCTP. To localize the mutationsthat accumulate spontaneously in a functional gene of such amutator phenotype, independent CSA7 mutants of the hypoxanthine–guaninephosphoribosyl transferase (hprt) gene were isolated and screenedby a polymerase chain reaction–single strand conformationpolymorphism technique. Sixty-two percent of mutants produceddetectable changes of the strand migration profile and the mutationswere preferentially localized in the exons 3 (31%) and 6 (62%).The sequencing of such exons revealed that the rate of C baseincorporation was the major mutation pathway and that the Abase of a GGA sequence was the preferential site of misincorporation. ³To whom correspondence should be addressed     

Peripheral nerve involvement in Churg-Strauss syndrome

Summary Peripheral neuropathy associated with bronchial asthma, multisystem organ dysfunction and idiopathic hypereosinophilia may be found in Churg-Strauss syndrome, hypereosinophilic syndrome and polyarteritis nodosa. Some authors have diagnosed their patients according to the presence in tissue biopsies of the three histological criteria of Churg and Strauss (necrotizing vasculitis, tissue eosinophilic infiltration, extravascular granulomas). We have observed three patients with a common history of a prodromal phase of allergic diseases (bronchial asthma and rhinitis) followed by a vasculitic phase with mononeuritis multiplex, purpura and arthritis, associated with hypereosinophilia of more than 1500 cells/mm³. All responded well to steroid treatment. Sural nerve biopsy revealed true vasculitis in two of these cases and a mild perivascular inflammatory infiltration in the other. On the basis of their characteristic clinical pattern, we think that our cases best fit the diagnosis of Churg-Strauss syndrome even though the typical histological features were not found in the sural nerves examined.     

Tuberculosis infection and disease in immigrant children

From the second half of the eighties, the cases of tuberculosis (TBC) in Italy have been constantly increasing. The increase in TBC cases in developed countries is related to different factors, including HIV epidemic and increased number of immigrants from countries with high TBC incidence and important socio-economic problems. Compared with adults few children with TBC were homeless or coinfected with HIV, nonetheless the children lived frequently in low socioeconomic status and consequently high risk of being uninsured and with adults at risk for tuberculosis (immediate relative, household members, or recently immigrated). An epidemiologic study was carried out, in order to evaluate the impact of TBC infection in immigrant children. From January 2001 to December 2002, Mantoux test (5 IU) was performed in immigrant children hospitalized or followed in two children hospitals. They included 228 children: mean age 4 years (range 1 month to 15 years). The patients came from: South America (44%) (especially from Ecuador), from Africa (20%), from Eastern Europe (19%), (especially from Middle East and North Africa), from Far East (17%). In 30 cases (13,2%) Mantoux test was positive. Among these latter, 21 presented latent infection, whereas another 9 had tuberculous disease with pulmonary localization and one of them associated with cervical adenopathy. In the study period, among all children (4426) admitted the two Units, the prevalence of tuberculous disease was 2,5% in immigrant children compared 0.2% in native children. Accurate epidemiologic monitoring, further clinical studies aimed at highlighting TBC peculiar aspects in children, and adequate therapy can lead to TBC control in the immigrant children.