Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971-1991).

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.

Standard conditioning regimen and T-depleted donor bone marrow for transplantation in chronic myeloid leukemia.

Between January 1984 to June 1985, 18 Ph1 positive chronic myeloid leukemia (CML) patients in chronic phase (CP) underwent allogeneic bone marrow transplantation (BMT) from HLA identical and MLC negative siblings. The median age was 32.5 yr and median disease duration of CML at time of BMT was 19.3 months. The pretransplant conditioning regimen consisted of cyclophosphamide (CTX) (120 mg/kg) and 10.20 Gy total body irradiation (TBI) at 6 doses of 1.7 Gy each, administered in 3 daily fractions over 2 days at a dose rate of 15-20 cGy/min. To prevent graft-vs-host disease (GvHD) we used methotrexate (MTX) in one patient and cyclosporin-A (CYA) in the other 17 patients. In addition to CYA, given until day +365, 10 patients received donor marrow depleted of T cells with CAMPATH-1. The residual marrow lymphocytes were always less than 1%. The rate of engraftment was significantly correlated with the number of nucleated cells infused. Neither GvHD nor graft failure were observed among CAMPATH-1 patients. In this group one cytogenetic and one hematologic relapse occurred. The overall actuarial survival at 24 months is 78%. Of the 10 patients treated with donor marrow depleted of T cells, 9 are alive after a median follow-up of 9 months (range 5-18), with an actuarial survival of 90%. Of the other 8 patients transplanted with untreated marrow, 5 are alive after a median follow-up of 19.3 months (range 3.7-24) and the actuarial survival is 63.8%. This pilot study seems to demonstrate that T-cell depletion of donor bone marrow with CAMPATH-1 is effective to prevent GvHD, while the risk of graft failure can be avoided using a "standard" conditioning regimen including a fractionated TBI with a fast dose rate and a prolonged administration of CYA at the maximum tolerable dosage. While the high frequency of relapses suggests the employ of more aggressive anti-leukemic conditioning regimens in CAMPATH-1 treated marrow recipients.

Autologous bone marrow or peripheral blood stem cell transplantation for patients with chronic myelogenous leukaemia in chronic phase.

The progressive and fatal course of chronic myelogenous leukemia has not been affected significantly by chemotherapeutic agents that control the benign phase of the disease. Combination chemotherapy and aggressive treatments may offer some advantages: however, these approaches do not appear to produce stable suppression of Ph1 chromosome or to prolong chronic phase and survival of these patients. Only allogeneic bone marrow transplantation has been demonstrated to be capable of inducing a stable, complete suppression of Ph1+ cells. Recently alpha Interferons (IFN) have been shown to control myeloid proliferation in patients with CML and to determine a progressive and persistent decline of Ph1+ bone marrow cells in some cases. The hypothesis that in most newly diagnosed patients with CML various amount of Ph1 negative cells must still be present, albeit in suppressed state in the bone marrow (BM) or in the peripheral blood (PB), have led some Authors to treat patients with high-dose chemotherapy followed by reinfusion of stem cells collected at diagnosis or after a response to cytoreductive treatments. We report 34 patients with CML treated in chronic phase with Busulohan and Melphalan conditioning regimen followed by reinfusion of BM or PB stem cells.

Comparative merits of thoracoscopy, mediastinoscopy, and mediastinotomy for mediastinal biopsy.

Between April 1992 and April 1993, we performed fifty-four mediastinal biopsies in 51 patients with a mediastinal mass. Nine of these had lung cancer with mediastinal lymphadenopathy, and the remaining 42 had various primary mediastinal lesions. We have performed twenty video-assisted thoracic surgical procedure, twenty-six mediastinoscopies, and eight anterior mediastinotomies. In 3 patients the diagnosis was not obtained by mediastinoscopy, and video-assisted thoracoscopy was performed. We conclude that mediastinoscopy is indicated for the majority of lesions involving the peritracheal space. Restaging of lymphoma and highly infiltrative lesions are better managed by video-assisted thoracic surgery. Anterior mediastinotomy is indicated when feasible under local anesthesia for tumors infiltrating the anterior chest wall. In all other cases video-assisted thoracic surgery is preferable because it allows removal of large tissue biopsy specimens and even resection with wide surgical exposure and low operative trauma.

Simultaneous occurrence of large B-cell non-Hodgkin lymphoma and myelodysplastic syndrome rapidly evolving into acute myeloblastic leukemia.

We describe a case of simultaneous occurrence of large B-cell non-Hodgkin lymphoma and myelodysplastic syndrome in the absence of previous chemotherapy or radiotherapy. After initiation of steroid treatment, the myeloid clone showed a rapid increase in both the bone marrow and peripheral blood with transformation into acute myeloid leukemia. The diagnosis were confirmed by immunophenotypic studies performed in the histologic sections of the lymph node, as well as in bone marrow and peripheral blast cells. This case may be indicative of potential down-regulation of a malignant myeloid clone induced by the malignant lymphoid clone.

[Comparison of metroplasty by Strassman's method and by Tomkins' method. Retrospective study of 30 years]. / Confronto tra metroplastica sec. Strassman e sec. Tompkins. Studio retrospettivo di 30 anni.

The study aimed to evaluate the usefulness of metroplasty to improve gestational ability in the presence of uterine malformations. From the analysis of results, it is clear that this surgical operation is undoubtedly efficacious when performed in selected patients (earlier negative obstetric outcome). The comparison of the two techniques (Strassman vs Tompkins) confirms that the latter produced better results in this series of patients.

[Cervix cerclage. A 20-year case load]. / II cerchiaggio cervicale. 20 anni di casistica.

Uterine cervical incompetence is the most common cause of habitual abortion in the second trimester of pregnancy and premature delivery; cervical cerclage still represents the only surgical treatment for cervical incompetence. In the last 20 years (1971-1990) we performed 272 Mac Donald cervical cerclages in patients between the 8th and the 34th week of pregnancy. In 16 cases the outcome of pregnancy is unknown; 198 women (73.3%) subsequentely delivered healthy infants later than 37 weeks' gestation or weighing more than 2500 g.

[The use of sulprostone for voluntary interruption of gestation and in intrauterine fetal death]. / Sull'impiego del Sulprostone nella IVG e nella morte endouterina del feto.

The paper attempts to assess the efficacy of Sulprostone as a preoperative dilator of the uterine cervix in the +VIG operations performed both before and after the 90th day of amenorrhea and in cases of intrauterine fetal death. From January to September 1987, 271 cases of VIG before the 90th day of amenorrhea, 2 cases of VIG after the 90th day of amenorrhea, and 3 cases of intrauterine fetal death were operated at Vercelli Midwifery School. Sulprostone, a synthetic prostaglandin, was shown to be a valuable aid on the basis of the results obtained and the slight side effects observed.

[Early puerperal depression: the puerperal blues]. / La depressione puerperale precoce: i blues puerperali.

The incidence and morbidity factors as regards non-psychotic depression during the puerperium (puerperal blues or maternity blues or post-partum blues) has been investigated in 50 females at random. Puerperal blues was diagnosed as the presence of depression in keeping with Kellner's symptomatic questionnaire. Approximately two-thirds of women experience depression during the early puerperium. Primiparas, patients who have had traumatic delivery (cesarean delivery) and those who have had considerable traumatic experience during pregnancy, and/or presented a previous history of psychopathological disorders, are more subject to puerperal blues.

A case of struma ovarii in a 92-year-old woman.

A case of struma ovarii in a 92-year-old patient with altered thyroid function is reported.

[Adenocarcinoma of pancreas with situs viscerum inversus totalis]. / Adenocarcinoma del pancreas in situs viscerum inversus totalis.

A case of adenocarcinoma of the head of the pancreas in a patient with situs viscerum inversus totalis, an association described for the third time in literature, is reported. The possible coexistence of malformations of transposed organs and the specular anatomosurgical situation requires particular attention in the diagnosis and preoperative evaluation as well as a careful reorientation of the surgical perspective and a correct surgical conduct.

[Management of facial pain resulting from cancer in oral and maxillofacial surgery]. / Il trattamento del dolore facciale di natura oncologica in chirurgia oro-maxillo-facciale.

Pain, which is among the most prevalent symptoms experienced by cancer patients, must absolutely be treated. The most important biologic effects of this sort of pain plays on patients' psychosociality. This is in reference to the quality of pain, the amount of pain and to the character of the patients. Actually, pain only in appearance is presented as a symptom; it is usually a disease. Patient assessment, the use of anticancer therapies and systematically administered non-opioid and opioid analgesics are pivotal. Practical aspects of cancer pain treatment include both drug selection, method of analgesic administration: selection of the appropriate route, dose titration and an understanding of the management of side effects. Pain therapy includes another series of possibilities like the use of adjuvant analgesics, psychological therapies, physiatric techniques and invasive interventions such as the use of intraspinal drugs, neural blockade and neuroablative techniques. This kind of therapy must be employed at all times, whether the case may be resolved surgically or not. So we think that pain can be effectively treated. This study was carried out to obtain the correct therapeutic approach for facial cancer pain syndrome. The research was performed on seven women and thirteen men with a mean age of 58 years. All the patients' clinical appearances were standardized with care. Study participants included odontostomatologists and anesthesiologists with experience of controlling cancer pain. The sensation of pain was quantified by means of the Visual Analogue Scale (VAS) while their psychosocial ability was assessed with the Karnofsky Performance Scale (KPS). In this way the authors hoped to obtain a good quality of standardization. The study was performed for a period of two months. The conclusions are that Trans Epidermis Nervous Stimulation (TENS) offers positive results for variable periods and only in 60% of patients with a low level of pain. The use of antiphlogistic non-steroid drugs and of opioid drugs, with a particular management requested from the personal clinical status of each patient, result as being the most effective therapeutic resource. Such therapies must be employed, whether the case may be resolved surgically or not. Nevertheless it is necessary to realize that drugs or other therapies for cancer pain are independent and propaedeutic to each surgical approach. Finally, the use of opioids is addressed in the management of patients with pain that is refractory to other interventions. This approach can provide adequate relief to the vast majority of patients. We find the morphinomania risk in cancer pain patients is not scientifically wellfounded.

Deflazacort in thrombocytopenia: a comparison with prednisone.

Deflazacort is a new glucocorticoid which in previous studies was found to be about 0.8 times as potent as prednisone. Twelve outpatients affected by chronic idiopathic thrombocytopenic purpura, in whom the maintenance dose of corticosteroid had already been established, were given 6 mg deflazacort for each 5 mg prednisone equivalent. Effectiveness of deflazacort therapy was estimated on the basis of the results of platelet count, bleeding time, tourniquet test, and physical signs related to platelet function. Tolerability was evaluated on the basis of laboratory data, side effects, and body weight. Deflazacort was administered for 54--263 days (mean 114.5) and, at the same mean daily dose of prednisone, succeeded in keeping platelet number unchanged. As far as bleeding time, tourniquet test, and physical signs are concerned, deflazacort therapy gave a further improvement compared to prednisone. Both treatments were very well tolerated. The high number of white blood cells and neutrophils during prednisone therapy was restored to the normal range by deflazacort.

T-helper phenotype chronic lymphocytic leukemia (Thp-CLL): characterization of an Italian case with particular biological findings.

A patient with Chronic Lymphocytic Leukemia (CLL) characterized by an expansion of helper phenotype mature T lymphocytes is here described. The phenotype of these cells was OKT3+, OKT4+, Leu 9+, 5/9+, OKT8-, Tac- and functional studies showed a strong helper activity on B cell differentiation; an "in vivo" presence of an IgG-lambda paraproteinaemia has been demonstrated. Cytogenetic studies showed multiple clonal, numerical and structural rearrangements which included a tandem t(14;14) (q11;32) translocation. Hybridization showed HTLV I related specific bands indicating the presence of exogenous sequences related to prototype virus but derived from a different Retrovirus (HTLV 1c). The clinical course was aggressive and unsuccessful treatments with various polichemotherapeutic protocols, associated with multiple leukaphereses, were performed. The authors underline that despite the morphological, immunological, biological and virological heterogeneity, the common feature of T-helper CLL is the inexorable clinical course which needs a new therapeutic approach.

Reversal of long-standing iron deficiency anaemia after eradication of Helicobacter pylori infection.

Helicobacter pylori has been proposed as a major determinant in multiple gastric disorders. We describe the case of a young adult with a long-standing medical history of sideropenic anaemia and of oral iron consumption dependence with a chronic superficial H. pylori-positive gastritis. All other causes of sideropenic anaemia were carefully excluded. Histology showed a peculiar pattern of non-active H. pylori-positive gastritis. The bacterium was a non-VacA-producing strain. The first attempt at eradication caused a reduction in bacterial load and led to a partial normalization of haematologic variables without improving the ferritin level. A successful second course of eradication therapy completely reversed the anaemia and restored the iron deposit, which persisted at the 29-month follow-up. H. pylori infection can be involved in unexplained cases of iron deficiency anaemia in adults, and its cure can normalize the haematologic picture.

Application of fluorescence in situ hybridization in defining a complex t(9;21;22) Ph formation.

We describe the application of fluorescence in situ hybridization (FISH) in a case of suspected chronic myelogenous leukemia (CML), cytogenetically characterized by a t(21;22) with no clear involvement of chromosome 9. The dual color FISH technique, performed using specific painting probes for chromosomes 9,21,22 and a BCR/ABL translocation probe, enabled us to confirm the diagnosis of CML by detecting the BCR/ABL rearrangement on chromosome 22q and the involvement of chromosome 9 in a variant translocation t(9;21;22).

Langerhans' cell histiocytosis in adults: a clinical and therapeutic analysis of 11 patients from a single institution.

BACKGROUND: Langerhans' cell histiocytosis (LCH) is a rare disorder of uncertain etiology, characterized by a wide clinical spectrum and varied behavior. METHODS: This retrospective study analyzed 11 adult patients with a diagnosis of LCH observed at the study institution between April 1988 and March 1993. RESULTS: Based on the sites and extent of disease at diagnosis, patients were divided into four categories. Group A was comprised of four patients with unifocal bone disease who had surgical curettage. At last follow-up only 1 patient was in continuous complete response (CCR) at 29+ months. The other 3 patients recurred at 3, 12, and 30 months, respectively, after surgery and at last follow-up were found to be in CR at 16+, 48+, and 124+ months, respectively, after therapy with vinblastine (VBL) and high dose methylprednisolone (HDMP). Group B was comprised of three patients with multifocal bone disease. Two of these patients received VBL + HDMP; at last follow-up, 1 patient was in CCR 8 months after completion of therapy, and the other developed progressive disease 11 months later. The third patient was treated with interferon (IFN) and at last follow-up was in CCR at 35+ months. Group C was comprised of 2 patients with bone and visceral disease who were treated with etoposide (VP-16) + HDMP; at last follow-up, 1 patient was in CCR at 42+ months and the other patient, who had isolated vulvar recurrence 16 months later, was in CR with treatment with local IFN. Group D was comprised of two patients with lung and lymph node involvement, one of whom was treated with VP-16 + HDMP and the other with cyclophosphamide, doxorubicin, vincristine, and prednisone; at last follow-up, both were in CCR at 30+ and 71+ months, respectively. CONCLUSIONS: VBL + HDMP showed efficacy in patients with bone disease, in particular those treated for recurrent LCH after surgery. Therapy with VP-16 and HDMP was successfully employed in patients with visceral disease. IFN was effective both for localized disease and in patients with multiple bone lesions.

The role of all-trans-retinoic acid (ATRA) treatment in newly-diagnosed acute promyelocytic leukemia patients aged > 60 years.

BACKGROUND: To evaluate the role and toxicity of ATRA therapy in newly-diagnosed APL patients aged > 60 yrs, the outcome of 16 consecutive elderly APL patients observed between January 1990 and June 1996 were analyzed. PATIENTS AND METHODS: Their median age was 65.5 yrs (range 60-81 years), the male/female ratio was 7:9, and molecular biology analysis showed a PML/RARa rearrangement in all patients. Seven patients had a concomitant cardiovascular disease. ATRA 45 mg/sqm/day was given to all patients, and in 11 was associated with idarubicin (AIDA protocol); in two patients ATRA was associated with mitoxantrone + ara-C, while the remaining three patients received ATRA alone. RESULTS: Fourteen patients (87.5%) achieved CR, and two patients (12.5%) died during induction. Despite the high CR rate, eight episodes of severe cardiovascular complication were observed in seven patients, three of whom had previously had cardiovascular disease; in addition, three patients had sepsis (two bacterial and one fungal). As of 31 March 1997, 9 of 14 patients were still in first CR after a 19-month (range 7-64 months) median follow-up since attainment of the CR. One patient died in CR of a fungal complication and four patients relapsed after 8, 9, 23 and 35 months following CR: two of them achieved a second CR lasting seven and +15 months with ATRA alone. Of the nine patients still in first CR, only three have received the planned consolidation therapy and five have been in CR for more than 24 months (+25, +33, +34, +38, +63). CONCLUSIONS: Despite the fact that most of these patients received shorter consolidation treatments than do younger patients, the good results achieved in them might be considered an indication for modifying treatment schedules in order to reduce severe toxicity and improve protocol compliance.

Polymorphonuclear leukocyte transfusion for the treatment of sepsis in the newborn infant.

A therapeutic trial of transfusions with polymorphonuclear leukocyte concentrates was performed in newborn infants with bacterial sepsis proven by blood culture. With each transfusion, 20 ml/kg of a preparation obtained by continuous flow filtration leukapheresis, and containing 0.5 to 1 x 10(9) WBC, with less than 6% lymphocytes, was administered. Twenty newborn infants with sepsis received from 2 to 15 PMN transfusions. Results were compared with findings in 18 newborn infants with sepsis admitted during the trial period, and not treated because of unavailability of the PMN preparation (Group B). Infants with fulminant illness were excluded from both groups. Groups A and B were similar with respect to clinical characteristics and to etiology (in the majority cases a highly antibiotic-resistant Klebsiella). The mortality rate was significantly lower in Group A than in Group B in the whole series (10% vs 72%, P < 0.001), and also in the subgroups with birth weight equal or below 1,500 gm (10% vs 91%, P < 0.001). Major complications and associated conditions (i.e., necrotizing enterocolitis, meningitis, pneumonia, peritonitis, osteoarthritis, disseminated intravascular coagulation) were observed in 12 patients of Group B, and in only three infants of Group A. Untoward effects attributable to PMN transfusions were never observed. PMN transfusion was a highly effective therapeutic tool in our population of infected newborn infants.