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Biomedical subjects

F Mandelli

Publications and source records attributed to F Mandelli.

At least 523 records · Page 29Linked to original sources

Ganciclovir and standard high-dose immunoglobulins for the treatment of cytomegalovirus interstitial pneumonia in a bone marrow recipient.

A 47-year-old woman received an allogeneic bone marrow infusion because of chronic myeloid leukemia. Two months after the transplant she developed an interstitial pneumonia: bronchoalveolar lavage yielded cytomegalic cells with intranuclear bodies, and cytomegalovirus DNA was detected by in situ hybridization techniques. Ganciclovir and standard high-dose immunoglobulins were administered to the patient with resolution of the pneumonia. No relapse of pneumonia was observed after a 4-month follow-up. It seems that the favorable outcome of the potentially fatal pneumonia observed in this patient might be related to early diagnosis, and prompt administration of ganciclovir and standard high-dose immunoglobulins.

Bone Marrow Transplantation↗

High doses of ara-C and m-AMSA in the treatment of refractory acute non lymphocytic leukemia.

From November, '85 to March, '87, 17 patients (12 males and 5 females, median 28 years) with resistant or relapsed ANLL received HiDAC (3 g/m2 c.i. 3 hs every 12 hs, day 1-4) + m-AMSA (100 mg/m2 i.v. day 5-7) as salvage therapy: 8/17 patients (47.1%) achieved CR, 7/17 (41.1%) were resistant and 2/17 (11.8%) died during induction; 8/10 relapsed patients achieved a 2nd CR, while all 7 primary resistant patients failed to. Median period of PMN less than 0.5 x 10(9)/l was 28 days, median period of PLTS less than 30 x 10(9)/l was 25 days. All patients had infections during aplasia. Median CR duration was 6.6 months, while median survival of responders was 10.6 months. Two patients with severe induction-related complications relapsed after 2 and 5 months, respectively: 1 patient underwent BMT and relapsed after 21 months; 5 patients, 4 of whom had received a prior ABMT during 1st CR, underwent ABMT: 3 died from ABMT related toxicity and 2 relapsed after 8 and 18 months, respectively. We conclude that HiDAC + m-AMSA is highly effective in relapsed, but not in resistant patients with acceptable hematologic and extra-hematologic toxicity. The role and modalities of ABMT in prolonging a 2nd CR are at present controversial.

Adolescent↗

Long-term remission of T-lymphoid extramedullary blast crisis of chronic myelogenous leukemia following allogeneic bone marrow transplantation.

Extramedullary blast crisis (EBC) with T-lymphoid phenotype has been reported rarely and generally associated with extremely poor prognosis. We describe a case of T-lymphoid EBC in which long-lasting remission was observed following intensive chemotherapy and allogeneic bone marrow transplantation (BMT). Characterization of bone marrow (BM) and lymph node (LN) cells was performed by means of morpho-cytochemical, cytogenetic, immunophenotypic and molecular analyses. These showed, together with a marrow picture consistent with typical Ph'+ chronic myelogenous leukemia, the expansion of an early T-lymphoid (CD7+/TdT+) LN cell population exhibiting the same bcr rearranged pattern and an additional Ph' chromosome. At the present time, 33 months after BMT, the patient is alive and well, with persistent clinical, hematological, cytogenetic and molecular evidence of complete remission.

Adult↗

Defective antibody-dependent and lectin-induced polymorphonuclear cytotoxicity in patients with myelodysplastic syndromes.

A short-term 51Cr-release assay was employed to investigate polymorphonuclear leukocyte (PMN) antibody-dependent (ADCC) and phytohemaglutinin-induced (PHA-ICC) cytotoxicity against chicken erythrocytes in 28 patients with myelodysplastic syndromes (MDS). MDS patients PMN-mediated ADCC and PHA-ICC were significantly reduced when compared to normal donors. When the patients were subdivided according to the revised FAB classification, a reduction in PHA-ICC from the RAEB group and a progressive impairment of ADCC from RA to RAEB-t patients was observed. These abnormalities may be ascribed to a reduced number of effector cells or to a metabolic impairment of their cytolytic capacity. These PMN functional deficiences may contribute to the increased susceptibility to infectious diseases, irrespective of the presence of granulocytopenia.

Aged↗

Ceftriaxone and amikacin as single daily dose in the empiric therapy for febrile episodes in neutropenic patients.

One hundred thirty-three febrile episodes in 115 neutropenic patients with hematologic malignancies were empirically treated with ceftriaxone and amikacin in a single daily dose. An indwelling central venous catheter (CVC) was present in 44 cases. Septicemia was documented in 18 (41%) patients with CVC (13 gram-positive, 5 gram-negative and 1 fungus) and in 30 (34%) patients without CVC (19 gram-positive, 10 gram-negative and 2 fungi). Coagulase-negative staphylococcus was observed in 10 out of 19 blood isolates in the presence of a CVC and in 6 out of 31 blood isolates in patients without CVC. Empiric therapy was successful in 56.4% of cases. Improvement after the addition of vancomycin or teicoplanin was observed in 38.6% of cases with a CVC and in 13.5% of those without (p less than 0.02). Only two patients died from gram negative septicemia, and the substitution of ceftriaxone with another beta-lactam was necessary in only 6% of the cases. Empiric therapy with single daily-dose ceftriaxone and amikacin appears to be effective in febrile neutropenic patients; our data, however, show the high incidence of Staphylococcus epidermidis septicemia and the frequent need to add an anti-gram-positive drug in patients with an indwelling CVC.

Agranulocytosis↗

High-dose intravenous gammaglobulin (HDIVG): therapy of refractory ITP in adults and children.

We performed 56 HDIVG administrations in adults (26) and children (30) affected by idiopathic thrombocytopenic purpura with two different schedules: a five-day course at 400 mg/kg/d and a "bolus" 1 gr/kg. Forty-five cases were treated in preparation for surgical operations and eleven for bleeding episodes. Response to the five-day course in adults was good in 3/24, fair in 13/24, poor in 8/24, while in children it was good in 14/26, fair in 9/26, poor in 3/26. The difference between adults and children is statistically significant. None of the responder patients submitted to surgical operation needed platelet infusions during surgery. Response to the "bolus" schedule (6 cases) in adults was poor in 1 case and good in the other one, and in children, fair in 3 cases and good in the other one. In responder patients treated for bleeding episodes we obtained clinical improvement with hemorrhage arrest. In adults the treatment was well-tolerated, while in children we observed 3/30 mild side effects and 1/30 important side effect.

Adolescent↗

Results of two different conditioning regimens followed by ABMT in refractory acute lymphoblastic leukemia.

Thirty-one patients affected by advanced ALL entered this study. Twenty (1 in I CR, 9 in II CR, 6 in III CR and 4 extramedullary relapses) were treated with the BMVC conditioning regimen. Eleven (9 in II CR, 2 in III CR) received the Busulfan plus Cytoxan conditioning regimen. Asta-Z 7654-purged marrow was reinfused at day 0. Both protocols were well tolerated. Two patients treated with the BMVC regimen died in aplasia from sepsis; 1 patient died in CR 5 months after transplantation, 13 relapsed after a median time of 4 months (range 1-31). Four patients are in CCR with a median follow-up of 16 months (range 11-24). In the BU + CY treated group no toxic deaths were observed. Four patients relapsed after a median of 3 months (range 2-7) and 7 are in CCR with a median follow-up of 5 months (range 2-28).

Adolescent↗

Aspergillus colonization of the nose and pulmonary aspergillosis in neutropenic patients: a retrospective study.

Fungal infections are definitely increasing in neutropenic patients with hematologic malignancies. In view of a previous report on a likely correlation between nose cultures positive for Aspergillus spp. and pulmonary aspergillosis, a retrospective study on 306 consecutive neutropenic patients was performed. Twenty-six patients had one or more nose cultures positive for Aspergillus: thirteen of them developed pulmonary aspergillosis. On the other hand, only twenty out of the remaining 280 patients with negative nose cultures developed this fungal pneumonia (p less than 0.00001). Even if negative results do not obviously exclude the possibility of invasive aspergillosis, nose cultures positive for Aspergillus might prove helpful in predicting this fungal infection in febrile neutropenic patients.

Agranulocytosis↗

Intensification in post-remission treatment of adult acute non lymphocytic leukemia.

In an attempt to reduce the risk of leukemic relapse, different post-remission intensifications based on high-dose Ara-C (HiDAC) and autologous bone marrow transplantation (ABMT) were evaluated in patients with acute non lymphocytic leukemia in first remission and compared as to response and toxicity. Between September, 1985 and May, 1987, 34 patients in complete remission were eligible for our study. Induction therapy consisted of one or two courses of daunorubicin (DNR) and Ara-C (schedule 3 + 7). Fourteen patients receiving intensive post-remission chemotherapy with DNR + Ara-C (schedule 2 + 5), HiDAC + DNR, and ABMT following pretransplant BAVC conditioning entered the first pilot study. A high toxicity was observed and only 5 of them completed the full treatment plan. Thus the second pilot study used a single post-remission intensive course with HiDAC + m-AMSA and ABMT following cyclophosphamide plus TBI or BAVC. This approach was more feasible. The preliminary results show the usefulness of intensive post-remission therapy: in fact, all patients but one who completed the treatment program are still in continuous complete remission. A large number of patients and a longer follow-up are required to draw final conclusions.

Adolescent↗

Third-line chemotherapy with CAVP (CCNU, melphalan, etoposide and prednisone) in refractory Hodgkin's disease.

Thirty-one patients affected by recurrent Hodgkin's disease have been treated with an oral combination chemotherapy including lomustine (CCNU 90 mg/sqm, on day 1), melphalan (Alkeran, 7.5 mg/sqm on days 1-5), etoposide (VP-16, 100 mg/sqm on days 6-10) and prednisone (40 mg/sqm on days 1-10). MOPP and ABVD regimens administered sequentially or in alternating fashion had been employed as first choice treatment. The majority of patients had extranodal (80%) and a progressive disease resistant to previous chemotherapy (80%). Complete and partial remission were induced in 8 (26%) and 5 patients (16%), respectively, with an overall response rate of 42%. Median duration of complete remission was 10 months. Patients who did not respond to previous chemotherapies had a significantly lower complete response rate (16%). Myelosuppression was the most frequent complication, with one patient dying of a thrombocytopenic hemorrhage. The oral administration of drugs allowed good patients', compliance with treatment. CAVP is an effective regimen in the management of patients with refractory Hodgkin's disease and the results obtained are comparable with other third-line chemotherapies.

Adolescent↗

Treatment of recurrent promyelocytic leukemia with a combination regimen utilizing amsacrine, cytosine arabinoside and 6-thioguanine (AAT).

Nine patients with recurrent acute promyelocytic leukemia have been treated between July, 1984 and November, 1987 with a combination therapeutic regimen consisting of amsacrine, cytosine arabinoside and thioguanine (AAT). Complete remission was achieved in 5/9 patients, one person died in aplasia of hepatic failure, and the remaining 3 died from heart failure with resistant disease. The 5 patients who achieved CR were successively treated with allogeneic (n = 2) or autologous bone marrow transplantation (n = 3). As of December, 1988 there were only 2 patients still alive and in CR, both underwent autologous bone marrow transplantation. The duration of the second complete remission in these two patients is 48+ and 29+ months, respectively. Moreover the overall survival duration for these two patients is 88+ and 41+ months, respectively. These data confirm that the AAT regimen is useful in treating recurrent acute promyelocytic leukemia, a disease otherwise characterized by a catastrophic clinical course during the recurrent phase.

Adult↗

Adult acute lymphoblastic leukemia: description and analysis of long-term survivors. A retrospective study.

This retrospective study, including 118 patients with acute lymphoblastic leukemia (ALL) aged greater than 15 years, with a minimum follow-up of 6 years, was aimed at defining potentially "cured" adults with ALL. At present, 21 out of 92 patients who achieved complete remission (CR) are long survivors: 16 in first CR, off-therapy; 4 in 2nd CR (3 off-therapy); 1 in 3rd CR, on treatment. On the basis of available data, we tried to identify factors at diagnosis which might predict long-term survival: white blood cell (WBC) count on admission was the only significant prognostic factor for overall survival (p = 0.0002) and first CR duration (p = 0.0005). The survival hazard rate (risk of death from acute leukemia per day) reaches 0 between 8 and 9 years from diagnosis. From our data we can identify two groups of ALL long-term survivors: the first includes 16 patients in 1st continuous CR (CCR), 12 of whom in CCR for over 8 years may be considered "cured"; the second group comprises 5 patients, relapsing once or twice, alive in 2nd or 3rd CR.

Adolescent↗

In vitro effects of human recombinant alpha-2b interferon on Ph1+ chronic myelogenous leukemia cells maintained in long term marrow cultures: a functional and morphological analysis.

In this study in vitro results obtained with hu rec IFN-alpha 2b on Ph1+ stem cells from patients with chronic myelogenous leukemia in chronic phase (CML in CP) will be discussed: cells were incubated with different IFN concentrations (100, 1000, 10000 IU/ml) for different times (24, 96 hrs, 8, 15, days) and maintained in long term marrow cultures (LTMC); CFU-GM assay, cytochemistry and cytogenetic analyses were performed weekly. A high sensitivity of CML cells to the in vitro treatment with IFN was observed. Cell count in LTMC showed a progressive reduction inversely proportional to time of incubation and concentration of IFN; a marked decrease in colony growth was observed at the end of incubations and during the course of LTMC. Low concentrations of IFN permitted a morphological maturation and the expression of alkaline phosphatase. Cytogenetic analyses showed a marked reduction of mytoses in cultures treated with high concentrations of IFN as result of a combined cytostatic and cytolitic effect; the persistance of 100% Ph1+ cells in LTMC and in CFU-GM colonies might be related, as opposed to in vivo results, to different IFN exposure conditions or might be influenced by other factors.

Bone Marrow Cells↗

Flow cytometric measurement (H-1 Technicon) of microcytic and hyperchromic red cell populations in pediatric patients affected by hereditary spherocytosis (HS).

In 7 splenectomized and 21 non splenectomized pediatric patients with hereditary spherocytosis (HS), red cell size and hemoglobin concentration distribution (erythrograms) demonstrated the size and chromia degree of red cell populations. The H-1 Technicon graphic reports obtained in the analysis of HS blood showed a remarkable shift of the Hb concentration histograms to the right end of the x-axis, revealing the presence of a high percentage of hyperchromic red cells. The opposite shift was noted for volume histograms. Graphic findings were quantitated by a computerized program of the H-1 Technicon system. These data have enabled us to determine the percentage of microcytic and normocytic hyperchromic RBC. In particular, non splenectomized HS patients showed an increase in microcytic and hyperchromic RBC twice as high as that of splenectomized patients (data computed by erythrograms). Moreover, there is a significant difference (5.6%, p less than 0.01) between splenectomized and non splenectomized patients in the microcytic hyperchromic RBC percentage (data computed by special volume/hemoglobin concentration mapping).

Child↗

Recombinant alpha interferon in the treatment of low-grade non-Hodgkin's lymphoma: results of a cooperative phase II trial in 31 patients.

Thirty-one patients with advanced stage of favorable histology non-Hodgkin's lymphomas were entered into a multicenter phase II trial with recombinant alpha A interferon as single agent. Interferon was administered intramuscular in doses of 6 x 10(6)/IU/m2 three times per week for 12 weeks. Dose escalation was applied, in the absence of toxicities greater than WHO grade II, in patients not responding after 4 weeks. In responding patients treatment was continued at the same dose with a weekly maintenance schedule for 12 additional weeks. Objective responses (4 complete, 10 partial) were obtained in 14 of the 27 evaluable patients (52%). Median time to progression was 15 months for partial responders, while none of the complete responders has relapsed up to the present time. Toxicity was generally moderate and manageable. Treatment was discontinued in three patients because of side effects, and one patient refused therapy after 3 weeks. Our study shows that recombinant alpha A interferon has antitumor activity in patients with favorable histology non-Hodgkin's lymphoma.

Adult↗