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Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits. © 2018 The Authors

Objetivo El objetivo de este estudio ha sido evaluar si la suplementacion con eritropoyetina (EPO) permite una apropiada donacion de sangre autologa previa a una artroplastia electiva de cadera o rodilla, incluso en pacientes con niveles limite de hematocrito (Hcto) y hemoglobina (Hb). Material y metodo Desde enero de 2000 hasta diciembre de 2001 fueron incluidos en este estudio 66 pacientes que requirieron artroplastia total de cadera o rodilla, a quienes se habia inscrito previamente en un programa de autotransfusion preoperatoria. Los pacientes fueron clasificados en dos grupos teniendo en cuenta sus niveles de Hb: aquellos con un nivel de Hb 13 g/dl (grupo 2; 29 pacientes) no se les suministro EPO ni antes ni durante el programa de autotransfusion. A los pacientes de ambos grupos se les extrajo sangre una vez por semana durante un periodo de entre una y tres semanas, administrandoseles ademas hierro por via oral. En todos los pacientes se evaluaron los valores de Hb y Hcto antes de la primera extraccion de sangre (valores basales), en el periodo prequirurgico y al alta, registrandose ademas la cantidad de sangre recogida y transfundida para cada grupo. Durante el estudio se excluyeron 20 pacientes por no cumplir los criterios de inclusion (grupo 1, n = 12; grupo 2, n = 8). Finalmente, se analizaron estadisticamente los datos correspondientes a 46 pacientes (grupo 1, n = 25; grupo 2, n = 21). Resultados A pesar de que los valores basales de Hb y Hcto para el grupo 2 fueron significativamente mas elevados que para el grupo 1 (p Conclusiones La diferencia en los niveles basales de Hb y Hcto observada entre los dos grupos fue completamente corregida gracias a la administracion profilactica de EPO durante el programa de autotransfusion preoperatoria, el cual se desarrollo de forma adecuada incluso en aquellos pacientes con niveles limite de Hb y Hcto.

Purpose The aim of this study was to determine whether erythropoyetin (EPO) supplementation permits an adequate autologous blood donation prior to elective hip or knee arthroplasty in patients with boundary hematocrit and hemoglobin (Hb) levels. Materials and methods Between January 2000 and December 2001, sixty-six patients were included in this study who required total hip or knee arthroplasty and who had also been enrolled in a preoperative transfusion program. Patients were classified into two groups, taking into account their hemoglobin levels: those with Hb 13 g/dl (group 2, 29 patients) were not given EPO before or during the self-transfusion program. Blood was extracted from patients in both groups once a week for one to three weeks; all patients received oral iron supplementation. In all patients, median hemoglobin and hematocrit values were determined before the first blood extraction (baseline values), during the preoperative period and at discharge; a record was made of the amount of blood extracted and transfused for each group. Twenty patients were excluded during the study since they did not fulfill the inclusion criteria (group 1: n = 12; group 2: n = 8). Lastly, the data corresponding to 46 patients was statistically analyzed (group 1: n = 25; group 2: n = 21). Results Although the median baseline hemoglobin and hematocrit values for group 2 were significantly higher than those for group 1 (p Conclusions Differences observed in the baseline hemoglobin and hematocrit levels between the two groups were fully resolved thanks to the prophylactic administration of EPO during the preoperative self-transfusion program, which was concluded appropriately even for patients with boundary hemoglobin and hematocrit levels.

Sickle cell disease is associated with a wide range of clinical and laboratory findings depending on genetic modulators and environmental factors. The most severe forms of sickle cell disease occur in patients with the Bantu haplotype. The purpose of this study was to determine the hematological profile of Congolese patients with homozygous sickle cell disease during periods of remission.Hemograms were performed in two series of patients with sickle cell disease in remission, i.e., one including 89 patients with a mean age of 8.7 years and the other including 42 patients with a mean age of 8.9 years. Hemograms were performed using an automated counter and reticulocytes were counted manually on peripheral blood smears. Fetal hemoglobin level (HbF) was measured by chromatography (HPLC). The mean values obtained were compared with those obtained in a sickle-cell-disease-free control group. Some parameters were also compared with those obtained in a group of patients exhibiting complications of sickle cell disease.Hemograms in the first series of patients demonstrated the following values: Hb: 7.2 g/dl; Hct 23.1%, red cells: 2.47 tera/L, leukocytes: 14.9 giga/L; VGM: 95.3 fL; CCMH:30.3% L and platelets:345,3 giga/L. Blood count showed 30.4% of polynuclear neutrophils, 33% de lymphocytes, 0.8% of polynuclear basophiles, 14% of monocytes, 7.8% of polynuclear eosinophils and 14% of erythroblasts. Mean HbF level was 7.2% and reticulocytes were at 88%. In the sickle cell disease-free group, the leukocyte rate was almost three fold higher than in the patient group exhibiting sickle cell disease in remission even though rates were higher than during complications.Hemogram profiles in Congolese patients with sickle cell disease are similar to those reported in the literature for subjects exhibiting the Bantou haplotype. Leukocytosis was associated with esinophilia and monocytosis suggested a topical state and chronic inflammation.

Summary This retrospective epidemiologic study on 256 cases of Acute Promyelocitic Leukemia (APL) observed in 20 Italian hematology centers between 1980 and 1988 demonstrated that APL is different from the other acute non-lymphocytic leukemias (ANLL). The male/female ratio was 0.9; median age at diagnosis was 40 years (with 80% of patients between 15 and 54 years of age). The minimal annual incidence of APL in Italy per 1,000,000 inhabitants was estimated to be 0.6; an increased incidence was observed in spring and in autumn. The overall median survival duration of APL patients was 12.6 months. From an epidemiological point of view APL is a distinctive subtype of ANLL.

To provide specialists and general practitioners with a review of the more recent data about anthracycline-induced cardiotoxicity and diagnostic methods utilized to reveal it.Reviewers identified studies concerning anthracycline cardiotoxicity, with special emphasis to those dealing with its pathogenesis and tools utilized for diagnosing it, by searching MEDLINE and reviewing references for retrieved articles.Three different clinical patterns of cardiotoxicity were described: acute, chronic and late. Highly sensitive tests are necessary for evaluating, during the time, the cardiotoxic effects associated with anthracycline-based therapy and to predict the development of cardiac dysfunction. For this reason, endomyocardic biopsy and radionuclide-based angiocardiography are considered the "gold standard". However, the bidimensional echocardiography is the most commonly performed because of its high specificity and sensitivity combined with low costs.The peer review of the most recent scientific literature clearly demonstrate that cardiotoxicity is an important complication of anthracycline-based therapy and that the cumulative dose greater than 550 mg/m2 is the main independent risk factor. For the evaluation of anthracycline-related cardiotoxicity, bidimensional echocardiography remains still the easier and faster method.

Between January 1985 and December 1992, 104 consecutive patients with symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement5 cm and/or transfusional requirement or Hb10 g/dl and/or white blood cell (WBC) count20 x 10(9)/l and/or platelets1.0 x 10(9)/l] received low-dose Melphalan (2.5 mg/3 times/week) to evaluate the efficacy and toxicity of this approach. Among 99 evaluable patients, 66 (66.7%) achieved a response after a median time of 6.7 months: 26 (26.3%) had a normalization of all clinical and haematological parameters (complete response, CR) and 40 (40.4%) showed an improvement50% (partial response, PR). Thirty-three patients (33.3%) were resistant. Reversible haematological toxicity was the most common complication. Median durations of CR and PR were 28.4 and 26 months respectively: median survival of CR + PR patients was 71.2 months (95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the non-responders (log-rank test, P =0.002). In the multivariate analysis, the following variables were significantly associated with a shorter survival: anaemia [hazard risk (HR) = 2.7], WBC count20 x 10(9)/l (HR = 2.4) and not achieving any type of response, either partial or complete (HR = 3.9). In conclusion, Melphalan could be a promising first-line option for MMM patients with clinical or haematological symptoms requiring treatment.

Prophylactic platelet transfusions are usually administered to patients receiving myelotoxic chemotherapy when their platelet count falls below 20,000 per cubic millimeter. Some observations suggest that lower platelet counts can be appropriate in patients in stable condition, but the safety of lower thresholds is uncertain.We evaluated 255 adolescents and adults (age, 16 to 70 years) with newly diagnosed acute myeloid leukemia (but not acute promyelocytic leukemia), who were treated in 21 centers. One hundred thirty-five patients were randomly assigned to receive a transfusion when their platelet count fell below 10,000 per cubic millimeter (or 10,000 to 20,000 per cubic millimeter in those with a temperature above 38 degrees C, with active bleeding, or a need for invasive procedures), and 120 patients were assigned to receive a transfusion when their platelet count was less than 20,000 per cubic millimeter.Patients in the group with a threshold of 10,000 platelets per cubic millimeter received 21.5 percent fewer platelet transfusions than the patients in the group with a threshold of 20,000 platelets per cubic millimeter (P=0.001). The numbers of red-cell units transfused were not significantly different between groups. Major bleeding (defined as any bleeding more than petechiae or mucosal or retinal bleeding) occurred in 21.5 and 20 percent of patients, respectively (P=0.41), and on 3.1 and 2.0 percent of the days of hospitalization. One episode of fatal cerebral hemorrhage occurred in the group with a threshold of 10,000 platelets per cubic millimeter; none occurred in the other group (P= 0.95). Actuarial estimates of survival during induction chemotherapy, actuarial estimates of the absence of major bleeding, and the length of hospital stay were not significantly different in the two groups.The risk of major bleeding during induction chemotherapy in adolescents and adults with acute myeloid leukemia (except acute promyelocytic leukemia, which we did not study) was similar with platelet-transfusion thresholds of 20,000 per cubic millimeter and 10,000 per cubic millimeter (or 10,000 to 20,000 per cubic millimeter when body temperature exceeded 38 degrees C, there was active bleeding, or invasive procedures were needed). Use of the lower threshold reduced platelet use by 21.5 percent.

Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.

During the last decade, the availability of large numbers of cytokines and growth factors has greatly favoured the use of biotherapies in several haematological disease. For MM, the majority of clinical studies have dealt with the use of IFN-alpha. From these studies it appears that IFN-alpha has a definite role in the treatment of MM especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies or HDC followed by BMT procedures or PBSCI. Data on the use of EPO have consistently demonstrated the role of this growth factor in ameliorating the grade of anaemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Despite the large amount of experimental data indicating a role for IL-2 and IL-6 in controlling tumour growth, there are only a few clinical studies dealing with their use in MM. From these, it appears that IL-2 and anti-IL-6 antibodies should be further investigated as therapeutic tools useful in maintaining responses, because results show that they arrest tumour progression rather than aid, tumour regression. Finally, in the next years, there will be a wider diffusion of biotherapies in MM that should take into account the roles that IL-1 beta and TNF alpha play in myeloma cell proliferation and bone destruction and the finding that retinoic acid is capable of inhibiting the growth of human myeloma cells in vitro through modulation of IL-6 and its receptor.

The article reviews the therapeutic efficacy of alpha interferon (alpha IFN) in the management of myelomatosis. The data provided in the medical literature suggest that alpha IFN is a useful agent in the management of myelomatosis. In particular, its association to conventional induction therapies of previously untreated multiple myeloma (MM) patients may improve the overall response rate and probably increase the number of complete responders. On the other hand, even though alpha IFN alone, in some patients with previously untreated MM, may induce good objective responses, it remains certainly less effective than conventional chemotherapy. Moreover, in a small proportion of advanced MM patients, alpha IFN alone has induced objective responses. It is therefore possible that alpha IFN should be combined with other therapeutic modalities to improve the observed response rate in these patients. Finally, alpha IFN maintenance treatment seems to be one of the most promising therapies for patients with myelomatosis. However, the achievement of a "true" "plateau phase" after the induction treatment is certainly necessary to permit alpha IFN of prolonging the response duration as well as survival duration. The importance of the achievement of a "true" "plateau phase" is better emphasized by the good results obtained using alpha IFN after transplantation procedures.

Interferons (IFNs) are a family of biological response modifiers with a broad spectrum of action on cellular proliferation as well as immunoregulation. In the last decade, these properties have prompted several investigations of the effect of IFNs on various haematological malignancies. IFNs-alpha have been used most extensively. The response rate is dependent on the type of the disease. The most striking effects have been observed in hairy cell leukaemia and chronic myeloid leukaemia. In both these malignancies the results are well consolidated and indicate that IFNs-alpha have modified the natural history of the disease. Results of IFN therapy in low grade lymphoma, cutaneous T-cell lymphoma and multiple myeloma suggest a beneficial role of IFNs-alpha in the induction, as well as the maintenance, phase. The efficacy of IFNs is now widely confirmed in treating patients with essential thrombocythaemia or polycythaemia vera. However, the role of IFNs in the management of chronic lymphocytic leukaemia and myelofibrosis with myeloid metaplasia is still controversial.

Starting from May, 1991, 35 untreated myeloma patients entered a multicentric pilot study to evaluate the feasibility of a program of PBSC transplantation for previously untreated myeloma patients. The schedule was as follows: 2 cycles of VAD followed by CY, 7 g/mq+G-CSF (Granulokine, Roche) for 14 days, to increase and collect PBSC. The subsequent conditioning regimen was Melphalan+Busulfan followed by G-CSF. As maintenance R alpha-2 IFN was given, until relapse. The median follow-up is 14 months (4-22). On April 1993, 34 patients received at least 2 cycles of VAD, 27 were submitted to PBSC collection, 22 received conditioning regimen plus PBSC and 16 of them are in the maintenance treatment with IFN. Considering 28 patients for an intention to treat evaluation (35-7 in treatment), responding patients are 71% with 46% who achieved CR. White cells and platelets raised to1000/mmc and50,000/mmc after a median period of 10 and 13 days, from CY, and 11 and 14 days from transplant, respectively. Two patients relapsed, 2 others died while in PR because of CMV epatitis and candida pneumonia. The median number of CD34+ cells and CFU-GM was 24.75 x 10(6)/kg b.w. and 28.1 x 10(4)/kg b.w. respectively. In conclusion this treatment seems to be feasible and with low toxicity, but a longer follow-up is needed to evaluate the progression free survival of the high proportion of responding patients that we observed.

A total of 74 patients with poor risk AML (median age 36.7 years, range 4.5-60.6) received a single course of a regimen including mitoxantrone (6 mg/m2 intravenous bolus daily, days 1 to 6), etoposide (80 mg/m2 intravenous over 1 h, daily, days 1 to 6) and intermediate-dose Ara-C (1 g/m2 over 6 h, daily days 1 to 6). 28 patients had failed initial remission induction with daunorubicin and conventional doses of Ara-C, 16 patients had secondary AML and 30 patients had relapsed from initial remission (five within six months, 15 over six months and ten after autologous or allogeneic bone marrow transplantation). Overall 41/74 patients (55%) achieved complete remission, 26 (35%) had resistant disease and seven (10%) died of infection during marrow hypoplasia. A 4-day course of the same regimen was given as consolidation to patients in complete remission. Subsequent antileukemic therapy was individualized. Profound myelosuppression and pancytopenia were universal resulting in fever or documented infections in almost 100% of patient; major hemorrhagic complications occurred in 39% of patients. Extrahematologic toxicity was mild to moderate consisting mostly of nausea and vomiting, oral mucositis and transient liver and cardiac dysfunction. We conclude that the MEC combination chemotherapy program seems to be an effective antileukemic regimen for secondary and advanced AML, with acceptable toxicity.

It has recently been demonstrated that erythropoietin increases hemoglobin levels in anemia secondary to chronic renal failure. Some recent experiences have suggested a possible role in the treatment of anemia in patients with myelodysplastic syndrome (MDS).From April, 1990 to March, 1991, 16 patients (11 males and 5 females, median age 58.5 years) affected by low-risk myelodysplastic syndromes (MDS) were treated with recombinant human erythropoietin (rHuEPO) to ameliorate Hb levels and reduce transfusional requirement. All patients received high doses of rHuEPO (400 U/Kg s.c. twice weekly for 3 months). A partial response, defined as a stable increase in Hb levels1g/dL and/or a reduction in transfusional need50% lasting at least 3 months, was achieved by 5/16 patients. Those who responded received an additional course of treatment with rHuEPO at an increased dosage (600 U/Kg twice weekly for 3 months), and one of these five showed a progressive rise in Hb level up to normalization, while the other 4 remained stable. The treatment was well tolerated and no adverse reactions were observed.These results suggest that some patients with MDS may benefit from rHuEPO treatment.

Multiple myeloma still remains a fatal disease. However, in the last months new biological and clinical informations have been provided about this disease. In particular, the immunophenotype of myeloma cells seems indicate, in some patients, a clonal involvement of a stem cell in the pathogenesis of mieloma. Moreover, new biological insights concerning the cytokine network, have revealed a probable effect of some cytokines, such as IL6, IL3, IL4. Finally, new insights in the biology of multiple myeloma have been provided by studies of molecular biology and flow cytometry. As for therapy, the best conventional induction treatment still remains to be defined. In the last years, the increased use of alpha Interferon and new therapeutic modalities, such as transplantation procedures in multiple myeloma, open new hopes toward a cure of this disease. Therefore, in the future a better knowledge of the multiple myeloma biology, associated with a wider use of new effective therapeutic approaches will certainly improve the natural course of this disease.

Seventy patients with acute promyelocytic leukemia (APL) were characterized at the DNA level using genomic retinoic acid receptor-alpha (RAR-alpha) probes on Southern blot experiments. Sixty-two cases were defined as M3 according to the French-American-British (FAB) criteria, and eight had a diagnosis of microgranular or variant (M3v) APL. The use of two restriction enzymes and three probes exploring the second intron of the RAR-alpha gene allowed us to detect specific abnormal DNA fragments in every case, with clustering of rearrangements within the 20-kb intronic region between RAR-alpha exons II and III. A more detailed mapping of APL breakpoints was performed in 52 cases in which three EcoRI subregions of the RAR-alpha second intron were analyzed with corresponding probes. Comparison of clinical and hematological features in the three subgroups of patients with distinct RAR-alpha breakpoints did not show significant differences regarding age, peripheral blood (PB) counts, presence of coagulopathy, or FAB classification (M3 v M3v). Interestingly, a significant difference was observed in the M/F ratio of the three subgroups, with a higher incidence of rearrangements at the 5' end of the RAR-alpha second intron in female patients, and more frequent 3' breakpoints in males. The results of this study indicate that a unique genomic alteration consistently occurs on the 17q- derivative of the APL specific t(15;17) aberration. Moreover, the clinical relevance of RAR-alpha gene analysis both at diagnosis and in follow-up studies is further emphasized.

The data provided in the medical literature suggest that alpha-IFN is a useful agent in the management of myelomatosis. In particular, its combination with conventional induction therapies of previously untreated MM patients may improve the overall response rate and probably increase the number of complete responders. On the other hand, even though alpha-IFN alone, in some patients with previously untreated MM, may induce good objective responses, it certainly remains less effective than conventional chemotherapy. Moreover, in a small proportion of advanced MM patients, alpha-IFN alone has induced objective responses. It is therefore possible that alpha-IFN should be combined with other therapeutic modalities to improve the observed response rate in these patients. Finally, alpha-IFN maintenance treatment seems to be one of the most promising therapies for patients with myelomatosis. However, the achievement of a "true" plateau phase after the induction treatment is certainly necessary to permit alpha-IFN maintenance treatment to prolong the response duration. As for the prolongation of survival duration observed in the Italian study, it requires confirmation by the other ongoing randomized studies. In the future, a better understanding of the mechanisms of action of alpha-IFN, as well as the increasing use of other biologic response modifiers, will improve the therapeutic modalities utilized to treat myelomatosis and therefore lead to better control of this so-far-incurable disease.

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.

A dramatic improvement in the prognosis of multiple myeloma has been obtained since treatment with alkylating agents was introduced in the sixties. In recent years much effort has been made to ameliorate the obtained results by employing polychemotherapy schedules of treatment. However, no significant improvements with respect to the conventional melphalan-prednisone treatment, in terms of survival duration, have been observed. New therapeutic approaches, such as the use of biological response modifiers and the autologous or allogeneic bone marrow transplantation offer new perspectives for multiple myeloma patients. In this paper we discuss current trends in the therapy of multiple myeloma and of related complications.

The records of 268 consecutive patients with acute hypergranular promyelocytic leukemia, treated at 29 Italian centers between January 1984 and December 1987, have been reviewed to assess the incidence of early hemorrhagic deaths and the effectiveness of various antihemorrhagic treatments. Three separate groups were considered: 94 patients were treated with heparin, 67 with anti-fibrinolytics (tranexamic acid, epsilon-aminocaproic acid, or aprotinin), and 107 with supportive therapy alone. The overall incidence of early hemorrhagic death (within the first 10 days of treatment) was 9.4%, with no significant differences between the various groups. Similarly, there were no differences in complete remission rates or duration of survival. The consumption of packed red blood cells and platelet concentrates was similar for two of the groups, and there was a significantly greater use of platelet concentrates for heparin-treated patients. High blast cell counts on the day of admission were significantly associated with hemorrhagic death within the first 10 days. These counts, plus high blast cell counts and low platelet counts, were associated with death within 24 hours.

7167 Background: Recent data have shown the benefit of adding surgery to neoadjuvant chemoradiotherapy, however no data are available for multimodality treatment including surgery in elderly patien...

Seventy-six consecutive neutropenic patients with hematologic malignancies, admitted to the "Department of Hematology" of Rome between March and September 1986, were randomly assigned to receive either piperacillin (300 mg/kg in four divided doses) or ceftazidime (100 mg/kg in four divided doses) plus amikacin (15 mg/kg in two divided doses) whenever they developed a febrile episode (temperature greater than 38 degrees C thrice over 12 hours, not related to drugs or transfusions, or else temperature greater than 38.5 degrees C). After 72 hours of antibiotic therapy, in case of persistent fever, piperacillin or ceftazidime was added to the ceftazidime + amikacin or piperacillin + amikacin combination, respectively. The antibiotic treatment was, however, modified according to in vitro susceptibility if a positive culture was present. Success without regimen modification was observed in both antibiotic combinations in 52.6% of cases. Considering the empiric cross of antibiotics, the response rate reached 78%. Neither toxicity nor side effects were observed in the reported groups. Considering blood isolates, we observed a greater incidence of gram-positive organisms compared with gram-negatives (28 cases vs 5 cases, 84.7% vs 15.3% respectively). Fungal infections were documented in four cases, two in each group. Even though no statistical difference was found between the two groups as far as patients not responding to the first antibiotic combination are concerned, piperacillin seems to have had more efficacy (twelve patients responding to the addition of piperacillin vs seven patients responding to the addition of ceftazidime). Piperacillin + amikacin seems to be as effective as ceftazidime + amikacin in the empirical therapy of febrile episodes in neutropenic patients.

Patients with acute promyelocytic leukemia have a bleeding disorder which was thus far explained by a coagulopathy based on diffuse intravascular coagulation (DIC). We observed severe alpha-2-antiplasmin deficiency in a consecutive series of such patients. We postulate proteolysis rather than DIC, also because of increased turnover of 125I-alpha-2-antiplasmin, to be responsible for the coagulopathy. Alpha-2-antiplasmin deficiency may well contribute to the bleeding disorder in acute promyelocytic leukemia.

In 23 patients with Hemophilia B (variants: II B-, 5 BR and 7 B+) factor VII Activity (VII:C) and Antigen (VII:Ag), in correlation with Thrombotest were measured. Thrombotest was found prolonged in 14 patients (in 8 > x+3SD and in 6 >x+2SD). Factor VII:C was found reduced in 1/11 B-, in 2/5 BR and in 4/7 B+ variants. Factor VII:Ag was normal in all but one patient (a 5 years old boy). The ratio VII:C/VII:Ag was abnormal in 8 patients. In these patients factors II and X activities were always within the normal range. The discrepances between VII:C and VII:Ag may be due to: 1) very minor vitamin K deficiency (presence of small amounts of PIVKA-II), 2) an inhibition of factor VII activation by a factor IX “abnormal” molecule, and 3) the synthesis of an abnormal molecule of factor VII.

Starting from May, 1991, 35 untreated myeloma patients entered a multicentric pilot study to evaluate the feasibility of a program of PBSC transplantation for previously untreated myeloma patients. The schedule was as follows: 2 cycles of VAD followed by CY, 7 g/mq + G-CSF (Granulokine, Roche) for 14 days, to increase and collect PBSC. The subsequent conditioning regimen was Melphalan + Busulfan followed by G-CSF. As maintenance R alpha-2 IFN was given, until relapse. The median follow-up is 14 months (4-22). On April 1993, 34 patients received at least 2 cycles of VAD, 27 were submitted to PBSC collection, 22 received conditioning regimen plus PBSC and 16 of them are in the maintenance treatment with IFN. Considering 28 patients for an intention to treat evaluation (35 -7 in treatment), responding patients are 71% with 46% who achieved CR. White cells and platelets raised to > 1000/mmc and >50,000/mmc after a median period of 10 and 13 days, from CY, and 11 and 14 days from transplant, respectively. Two patients relapsed, 2 others died while in PR because of CMV epatitis and candida pneumonia. The median number of CD34+ cells and CFU-GM was 24.75 x 106/kg b.w. and 28.1 x 104/kg b.w. respectively. In conclusion this treatment seems to be feasible and with low toxicity, but a longer follow-up is needed to evaluate the progression free survival of the high proportion of responding patients that we observed.