G. Torlontano

Cytogenetics and bone marrow transplantation

The authors report hematologic and cytogenetic data on 19 patients treated with allogeneic bone marrow transplantation (BMT) for severe hematologic disorders: 8 patients with chronic myelogenous leukemia, 6 with acute leukemia, 3 with severe aplastic anemia, 1 with refractory anemia, and 1 with beta-thalassemia major. Cytogenetic assays were performed on marrow cells before conditioning, 30 days after BMT, and at subsequent times. The authors discuss the role of cytogenetic studies in the evaluation of bone marrow engraftment, leukemic transformation of the graft, and disease relapse.

Cytogenetic survey of 31 patients treated with bone marrow transplantation for acute nonlymphocytic and acute lymphoblastic leukemias

The authors report on a sequential cytogenetic study carried out on 31 patients with acute leukemia (20 with acute lymphoblastic leukemia and 11 with acute non-lymphocytic leukemia) who underwent bone marrow transplantation (BMT). Engraftment was documented in all patients with sex-mismatched donors and with donor constitutional aberrations. During the follow-up, ranging from 6 to 110 months, clinical and hematologic relapse was observed in 11 patients (35.5%). Five of these cases showed a normal karyotype, 3 were of undefined relapse origin, 2 were aneuploid karyotypes, and one was donor (male) metaphases. Cytogenetic and immunologic data in the latter patient were suggestive of relapse in donor cells.

Cytogenetic survey of 80 patients with acute nonlymphocytic leukemia

The authors report a cytogenetic survey of 80 patients with acute nonlymphocytic leukemia. The prognostic value of chromosome aberrations has been evaluated with three methods. The first one showed that patients with NN or AN bone marrow cellularity have a significantly better prognosis than those with AA cellularity; the second method confirmed the relatively good prognosis for patients with t(8;21) and abnormal 16 and a poor one for those with rearrangements of chromosomes 5 and/or 7. The authors also noted, surprisingly, that patients with hyperdiploidy had a significantly poorer prognosis than those with hypodiploidy and especially pseudodiploidy. The third method showed that patients with very complex karyotypes and a worse outcome than those with simple changes. Finally, they discuss the prognostic value of unusual and/or undeciphered chromosome changes detected in 18 patients, with a mean survival of 9.6 months, showing that these changes have a negative prognostic significance.

Detection of minimal residual disease by polymerase chain reaction in patients with different hematologic diseases treated by bone marrow transplantation

Thirteen male patients affected by different hematologic diseases who underwent bone marrow transplantation (BMT) with female donors were investigated by cytogenetic analysis and polymerase chain reaction (PCR) amplification of a DNA sequence specific for the Y chromosome. In six of these patients, PCR showed the presence of the Y chromosome-related sequence; in only three of these did cytogenetic analysis confirm the presence of mixed chimerism. In the remaining three patients, the results of the PCR were confirmed by in situ hybridization on cell nuclei with a probe for the alpha-satellite of the Y chromosome. We compare results obtained with the two methods and discuss the meaning of the minimal residual disease detected by PCR in patients submitted to BMT.

Leukemic evolution in three patients with myelodysplastic syndrome and unusual chromosome changes

The authors describe three patients with myelodysplastic syndrome without a history of exposure to chemical agents and who showed many chromosome rearrangements not previously reported in this hematologic disorder, and a rapid outcome of the disease. The authors discuss the significance of the chromosome changes, suggesting, in agreement with others, that patients with complex rearrangements have a poor prognosis.

Patterns of infection in 41 patients with idiosyncratic drug-induced agranulocytosis

SummaryWe examined the patterns of infection in 41 consecutive patients with idiosyncratic drug-induced agranulocytosis observed during the past 15 years. All patients were nursed in reverse isolation and treated prophylactically with oral antimicrobials and antifungal compounds. Nine of 41 patients remained without fever and did not need any parenteral antibiotic treatment for full recovery. The other 32 patients developed fever during the period of agranulocytosis and were treated with empirical antimicrobial therapy. Febrile episodes were documented microbiologically in 16 patients (eight with and eight without bacteremia) and clinically in six patients. In the other ten cases the fever was of unexplained origin. The observed pattern of infection was in accordance with the type of infection as reported in cancer patients during the granulocytopenic phase induced by cytotoxic drugs. Ten of 32 febrile patients showed improvement after empirical antimicrobial therapy, whereas three patients died, two of them of a lower respiratory tract infection and one of a massive hemorrhage due to necrosis of the carotid artery. In ten patients the signs and symptoms of infection resolved only after adjustment of the initial empirical scheme. In nine patients the fever persisted even after additional empirical antifungal therapy but subsided after recovery of the granulocytopenia.

Patterns of cytomegalovirus retinitis in immunocompromised patients treated with 9-(2-hydroxy-1-(hydroxymethyl)ethoxymethyl) guanine (ganciclovir).

Five immunocompromised patients, four with AIDS and one who had undergone bone marrow transplantation, showing ocular signs of cytomegalovirus retinitis, were treated with 9-(2-hydroxy-1-(hydroxymethyl)ethoxymethyl) guanine (Ganciclovir), given intravenously at the dose of 5 mg/kg twice daily for a period ranging from 10 to 20 days. At the end of the treatment, in 4 of 5 patients, the ophthalmoscopic picture had improved, with reduced exudation and an arrest in the progression of retinal necrosis, the pattern clearly indicating a trend towards organization and scarring. Complete resolution of the retinitis without subsequent relapse was observed only in the bone marrow transplant patient, who recovered immunologically, whereas improvement of the eye involvement was only transient in the three AIDS patients.

102 BONE MARROW TRANSPLANIATION FOR CHRONIC GRANULDMATDUS DISEASE X/b+

An 8 year old boy affected by a rare form of X-linked Chronic Granulomatous Disease (CGD) and present cytochrome b underwent successful bene marrow transplantation on August 1989 in Pescara 13.4 ×10 nucleated cells/Kg) from his 6 year old histocompatible sister (HLA-identical and HLC negative) after a preconditioning regimen of Busaifan (3.25 mg/kg/day for 4 days) followed by Cyclophosphamide (50 mg/kg/day for 4 days). The patient was protected by LAF isolator and by our decontamination protocol. Cyclosporme was administered for 12 months and oral Acyclovir for 270 days, The clinical course was uncomplicated and the boy was engrafted promptly with PMN counts normalizing or day +28 and the complete reversal of neutrophil function defect. Cytogenetic showed complete engraftment of donor origin at 4 months after BMt, Eighteen months after BMT the boy still continues to be free of infections. In fact NBT was already positive at the nirteth month for Zymosan (92%) and for PHA (91%), The 0% generation hith PMA was 8.88 nmol/min/10− cells and with fMLA was 13.01 nmol/min/106 cells. Cytochrome b spectra showed peals at 428, 530, 556 nm (7.81 pmol/106 cells) and all his neutrophils stained for cytochrome b on the cell surface by using monoclonal antibodies 7D5 (98%). Earlier atrespts of BMT for CGD by bone marrow from related or unrelated donors have failed either because of slow loss of the graft and gradual deterioration in neutrophil function or because of lethal infections and/or GvH disease. We conclude that as well as in CGD %/b-, previously described b/ us (Bone Narrow Transplant 4, 695, 1989;, a complete neutrophil engraftment can be achieved also in this rare form CGD X/b+.

Allogeneic Bone Marrow Transplantation for Chronic Myelogenous Leukemia Pescara Team Experience

Median survival of patients with chronic myelogenous leukemia (CML) is estimated about 36 months and have not changed substantially in the last two decades. Allogeneic bone marrow transplantation (BMT) has been demonstrated to be the only therapeutical approach capable of eradicating the Ph’-positive clone and offering a sustained possibility of cure. We report here our experience about BMT in CML.

Allogeneic Bone Marrow Transplantation for Thalassemia Major by Busulphan — Cytoxan Protocol and Cyclosporin — Acyclovir Prophylaxis

Although much progress is being achieved in transfusion therapy and iron chelating treatment, homozygous thalassemia patients have a bad quality and limited expectancy of life with conservative therapy. They usually dye by the second or the third decade because of myocardium and liver iron overload. Allogeneic bone marrow transplantation (BMT) has been demonstrated to be an efficacious form of therapy for patients with congenital bone marrow disorders. Essential to propose such form of therapy is to reduce at most the risk taken during the procedure. To this purpose, we have selected for BMT young thalassemic patients under 8 yr of age, little transfused, without parenchimal damage and with an HLA-identical and MLC-nonreactive sibling to serve as marrow donor.