[Artificial intelligence and its applications in medicine I: introductory background to AI and robotics]. / La inteligencia artificial y sus aplicaciones en medicina I: introducción antecedentes a la IA y robótica.

Technology and medicine follow a parallel path during the last decades. Technological advances are changing the concept of health and health needs are influencing the development of technology. Artificial intelligence (AI) is made up of a series of sufficiently trained logical algorithms from which machines are capable of making decisions for specific cases based on general rules. This technology has applications in the diagnosis and follow-up of patients with an individualized prognostic evaluation of them. Furthermore, if we combine this technology with robotics, we can create intelligent machines that make more efficient diagnostic proposals in their work. Therefore, AI is going to be a technology present in our daily work through machines or computer programs, which in a more or less transparent way for the user, will become a daily reality in health processes. Health professionals have to know this technology, its advantages and disadvantages, because it will be an integral part of our work. In these two articles we intend to give a basic vision of this technology adapted to doctors with a review of its history and evolution, its real applications at the present time and a vision of a future in which AI and Big Data will shape the personalized medicine that will characterize the 21st century.

Effectiveness of a chat-bot for the adult population to quit smoking: protocol of a pragmatic clinical trial in primary care (Dejal@).

BACKGROUND: The wide scale and severity of consequences of tobacco use, benefits derived from cessation, low rates of intervention by healthcare professionals, and new opportunities stemming from novel communications technologies are the main factors motivating this project. Thus, the purpose of this study is to assess the effectiveness of an intervention that helps people cease smoking and increase their nicotine abstinence rates in the long term via a chat-bot, compared to usual practice, utilizing a chemical validation at 6 months. METHODS: Design: Randomized, controlled, multicentric, pragmatic clinical trial, with a 6-month follow-up. SETTING: Healthcare centers in the public healthcare system of the Community of Madrid (Madrid Regional Health Service). PARTICIPANTS: Smokers > 18 years of age who attend a healthcare center and accept help to quit smoking in the following month. N = 460 smokers (230 per arm) who will be recruited prior to randomization. Intervention group: use of a chat-bot with evidence-based contents to help quit smoking. CONTROL GROUP: Usual treatment (according to the protocol for tobacco cessation by the Madrid Regional Health Service Main variable: Continuous nicotine withdrawal with chemical validation (carbon monoxide in exhaled air). Intention-to-treat analysis. Difference between groups in continuous abstinence rates at 6 months with their corresponding 95% confidence interval. A logistic regression model will be built to adjust for confounding factors. RESULTS: First expected results in January 2020. DISCUSSION: Providing science-based evidence on the effectiveness of clinical interventions via information technologies, without the physical presence of a professional, is essential. In addition to being more efficient, the characteristics of these interventions can improve effectiveness, accessibility, and adherence to treatment. From an ethics perspective, this new type of intervention must be backed by scientific evidence to circumvent pressures from the market or particular interests, improve patient safety, and follow the standards of correct practices for clinical interventions. TRIAL REGISTRATION: ClinicalTrials.gov, reference number NCT03445507.

Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age

An experience in integrated management of clinical risks.

BACKGROUND: Manage clinical risks under the integrated risk management model of the BUPA organization (British United Provident Association). MATERIALS AND METHODS: BUPA is an international group that provides health insurance and healthcare services. The project has been limited to Europe and Latin America (ELA) and this article presents the results related to hospitals. The integral risk management model was based on a governance structure, a risk management framework and the risk management itself (continuous process of identification, evaluation, management, monitoring and reporting). For the latter, a catalog of potential clinical risks was drawn up, using the Joint Commission International (JCI) standards as a reference and applied to a hospital to identify the risk to which they were exposed in their daily activity. An evaluation was conducted, based on its impact and probability of occurrence and depending on the residual and inherent score obtained, the action on each risk and the effectiveness of the controls were determined. A continuous monitoring of the risk profile and the information to share with the Board was defined. RESULTS: The catalog consisted of 126 risks and 479 controls, divided by areas of application. In the assessment of the inherent risk, 84% of the risks were at an acceptable and assumable level, and in 16% it was necessary to establish an action plan. CONCLUSIONS: Under the conditions of the study, we believe the benefits of implementing an integrated management of clinical risk system consisted in providing services that meet the legal requirements and standards of good practice (in our case, the JCI's standards). They allowed us to advance in the organization's management of, improving its efficiency in the allocation of resources for risk management and adaptation to the environment and the patient. In addition, this strategy can facilitate decision-making and encourage the organization's transformation capacity.

Relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: outcome and prognostic factors: the Chronic Myeloid Leukemia Subcommittee of the GETH (Grupo Español de Trasplante Hemopoyético).

In order to analyze the outcome of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT), we investigated data from 107 patients reported to the Spanish Registry, GETH. In all, 93 (87%) patients were treated after relapse; 36 out of 49 that failed to achieve a response received a second relapse-treatment, and seven a third one. At the last follow-up, the number of patients in molecular or cytogenetic remission was 29 and 13, respectively. Overall survival and progression-free survival after relapse were 53.6% (95% CI: 42.9--64.2) and 52% (95% CI: 41-63) at 5 years, respectively. In multivariate analysis, survival was significantly related to CML phase at relapse (cytogenetic or chronic phase vs advanced phases) and time from transplant to relapse (<1 vs >or=1 year). Patients with no adverse factors had a better survival compared with patients with one or two adverse features (65 vs 35 vs 0%, respectively). We conclude that a significant proportion of CML patients that relapse after transplantation can regain complete and long-lasting remissions with one or more salvage therapies. Disease stage at relapse and time from transplant to relapse should be taken into account when comparing results of different salvage treatments.

The role of hepatitis C and B virus infections as risk factors for severe liver complications following allogeneic BMT: a prospective study by the Infectious Disease Working Party of the European Blood and Marrow Transplantation Group.

BACKGROUND: Severe liver disease, including fulminant hepatic failure and venoocclusive disease can occur after bone marrow transplantation (BMT). The aim of our study was to assess risk factors for veno occlusive disease and severe liver disease occurring within 6 months from BMT. METHODS: A total of 193 consecutive patients from 15 BMT Centers were prospectively enrolled between January and June 1995. Data on donors and recipients before and after transplant were collected and included age, gender, alanine aminotransferase (ALT), hepatitis B (HBV), and hepatitis C virus (HCV) markers, hematological disease, status and type of BMT, conditioning regimen and graft versus host disease prophylaxis. Statistical analysis included univariate descriptive and multivariate analysis based on logistic regression on major end-points. RESULTS: Forty-three of 193 patients died during the study period, and liver disease was the main cause of death (13 of 43, 30%). Incidence of severe veno occlusive disease was 8%, fulminant hepatic failure 0.5% and 12% of cases had ALT >500 U/L (normal < or =42 U/L). A de novo HBV or HCV infection occurred in 3.2 and 7% of patients respectively. Predictive risk factors for life-threatening liver disease were: unrelated donors (relative risk=5.8, confidence interval=1.7-19.8) and abnormal BMT donor ALT (relative risk=6.3, confidence interval=1. 5- 25.5). CONCLUSIONS: This study indicates that ongoing or previous infection with HBV or HCV in donor or recipient is not an absolute contraindication for BMT. However, abnormal ALT levels in BMT donors were a significant predictor of potentially lethal liver complications. The occurrence of de novo HBV or HCV infection did not correlate with severity of liver disease observed in the first 6 months posttransplant. These findings should be carefully evaluated before disregarding HBV or HCV positive siblings with normal transaminase levels in favor of unrelated donors.

High dose busulfan and seizures.

Three cases of busulfan-associated convulsions in 28 bone marrow transplant recipients are reported. Convulsions occurred in spite of anticonvulsant prophylaxis in two of the three cases. Fits were generalized; no neurological deficit was found after the episodes and there were no recurrences. Although conditioning regimens including busulfan are used increasingly only rare cases have been reported and little mention of this side effect is made. We emphasize that convulsions are not infrequent side effect of conditioning regimens including high dose busulfan, and efficient anticonvulsant prophylactic regimens should be used.

Nephroprotective effect of cilastatin in allogeneic bone marrow transplantation. Results from a retrospective analysis.

Cilastatin, an inhibitor of the tubular brush border enzyme dehydropeptidase-I, is added in a fixed combination to imipenem. Cilastatin has been demonstrated in different animal models and in one clinical trial, to reduce the nephrotoxicity associated with cyclosporin A. To evaluate a possible nephroprotective effect of cilastatin following allogeneic BMT we conducted a retrospective analysis of 104 patients transplanted in our BMT Unit from January 1991 to January 1995. Imipenem/cilastatin (I/C) was used in a non-randomized manner in 64 patients during this period. Acute renal failure (ARF) was diagnosed in 32 patients (30%). ARF was not associated with gender, sepsis, conditioning regimen, underlying disease, bilirubin, or age. VOD occurred in 12/32 (37.5%) of patients with ARF whereas it occurred in only 7/72 (9.7%) of patients without ARF (P < 0.0007). ARF was not correlated with use of aminoglycosides, vancomycin, ciprofloxacine, ceftazidime or amphotericin-B. However, 13 patients of 64 exposed to I/C (20.3%) developed ARF vs 19 of 40 patients (47.5%) who were not exposed to I/C (P < 0.003; OR 0.28). Stratified analysis and multiple logistic regression confirmed the I/C nephroprotective action. The mean cyclosporin A levels in the I/C group were significantly decreased (208.6 +/- 64.9) vs the non-I/C group (265 +/- 118). We conclude that these results suggest I/C may counteract acute cyclosporin A nephrotoxicity following BMT and further prospective clinical trials are needed to confirm if routine administration of cilastatine confers benefit in the BMT setting.

Transplantation of allogeneic CD34-selected peripheral stem cells does not prevent transmission of hepatitis C virus from an infected donor.

There is little information on the clinical course of transplantation from HCV-positive donors. However, it seems that there is no increased risk of acute liver failure after the procedure and that the presence of HCV-RNA in serum is necessary for transmission to take place. We report a case of allogeneic CD34-selected peripheral stem cell transplantation from an HCV-infected donor with viremia with a special clinical and virological course. After the selection procedure and cell washing we could not detect HCV-RNA by PCR in the wash buffer, but HCV-RNA was positive by PCR in the selected cells. Once the patient received the transfusion of the selected product HCV was detected in the PBMCs and at very low concentration in serum. HCV was also demonstrated in the hepatocytes with the in situ hybridization technique. In conclusion, we have shown that CD34+ cell selection from an HCV-positive allogeneic donor does not prevent HCV infection in the recipient. Our results also suggest that HCV replicates in PBMCs in vivo and that these cells release viral particles that can infect the liver.

Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT.

We report a 54-year-old woman who received interferon alpha for haematological relapse of Ph-positive CML, 7 years after allogeneic BMT from an HLA-identical brother. Eighteen months after relapse, cytogenetic and molecular remission was achieved. She received interferon therapy for 25 months and it was discontinued when she developed skin lesions on her face and trunk, dysphagia and fever with respiratory failure and bilateral patchy airspace consolidation of the lung without microbiologic findings. Histologic features showed discoid lupus erythematosis, oesophagitis with pseudomembranes and a mixed pattern of lymphocytic bronchiolitis involving the alveoli and interstitial spaces all compatible with chronic GVHD. The patient was commenced on immunosuppressive therapy with complete clinical and radiological resolution. The available evidence supports an atypical presentation of chronic GVHD and suggests a role for interferon alpha in the pathogenesis of GVHD. To the best of our knowledge, this is the first case reported of severe chronic GVHD occurring during the course of interferon therapy for relapsed CML.

Allogeneic bone marrow transplantation for high risk acute lymphoblastic leukemia. Results from a single institution.

We present our experience with bone marrow transplantation (BMT) in 30 consecutive patients with high risk acute lymphoblastic leukemia. With a median follow-up of 4 years the disease-free survival (DFS) was 44% for the whole group, with a significant difference between patients in first or second complete remission (CR 1 and 2, as one group), compared with patients with more advanced disease (greater than CR2), 69.5% versus 15.4% (p less than 0.01). The main cause of BMT failure was leukemic relapse, with a relapse rate of 15% for patients in CR 1 and 2 and of 77% for patients with greater than CR2 (p less than 0.01). Among patients with active disease at BMT those who had 15% blast cells or less in the marrow fared better than those with more advanced disease or extramedullary relapse. Transplant-related death was 17%. Graft-versus-host disease (GVHD) was associated with an antileukemic effect; the DFS for patients with acute and/or chronic GVHD was better than for patients with no GVHD at all.

Detection of hepatitis G virus from serum and liver of a patient with long-term liver dysfunction after autologous bone marrow transplantation.

Long-term effects after blood or bone marrow transplantation (BMT) are emerging as an important issue, as more patients are included in BMT programmes and as this procedure becomes more successful. Long-term liver dysfunction, mainly due to chronic graft-versus-host disease or hepatitis C virus infection, is a well-known complication. Nevertheless, the diagnosis of liver disease in this patient group is sometimes difficult and, despite adequate studies, it may remain undetected. A novel hepatitis-associated virus, hepatitis G virus (HGV), has recently been identified. The virus belongs to the Flaviviridae family and is known to be parenterally transmitted, although there is no clear evidence to implicate this agent in causing acute or chronic hepatitis. We report a patient who developed mild, but persistent, abnormalities in transaminases for 2 years after an autologous BMT. HGV RNA was detected in both serum and liver. HGV RNA persisted in serum for at least 8 months. No other known hepatitis virus was found. This report provides the first direct evidence of a patient with long-term liver abnormalities after a BMT in whom the only known hepatitis virus isolated was the HGV.

Long-term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients.

This retrospective study has aimed at determining the prevalence, aetiology and clinical evolution of chronic liver disease (CLD) after allogeneic bone marrow transplantation (BMT). A total of 106 patients who had been transplanted in a single institution and who had survived for at least 2 years after BMT were studied. The prevalence of CLD was 57.5% (61/106). In 47.3% of cases more than one aetiopathogenic agent coexisted. The causes of CLD were iron overload (52.4%), chronic hepatitis C (47.5%), chronic graft-versus-host disease (C-GVHD) (37.7%), hepatitis B (6.5%), non-alcoholic steatohepatitis (NASH) (4.9%), autoimmune hepatitis (AIH) (4.9%) and unknown two (3.3%). Twenty-three patients with iron overload underwent venesections which were well tolerated. An improvement in liver function tests (LFTs) was observed in 21 (91%) patients. All six patients with siderosis as the only cause of CLD normalized LFT as well as three patients with HCV infection. Clinical evolution was satisfactory for patients with GVHD, AIH, NASH and hepatitis B. At the last visit 23 patients continued with abnormal LFTs, and 19 of them were infected by the HCV. A sustained biochemical and virologic response was achieved in only one case out of six patients with CHC who received interferon. We have found that CLD is a common complication in long-term BMT survivors. The aetiology is often multifactorial, iron overload, CHC and C-GVHD being the main causes. The CLD followed a rather 'benign' and slow course in our patients as none of them developed symptoms or signs of liver failure and we did not observe an increase in morbidity or mortality in these patients, but a longer follow-up is necessary in HCV infected patients based on the natural history of this infection in other populations.

Results of a pilot study of 40 patients using high-dose therapy with hematopoietic rescue after standard-dose adjuvant therapy for high-risk breast cancer.

The study was designed to determine the toxicity, feasibility, and effectiveness of high-dose cyclophosphamide (6 g/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2 (CTCb) with hematopoietic rescue as consolidation after standard-dose adjuvant chemotherapy treatment of primary high-risk breast cancer. From October 1991 to September 1994, 40 patients with stage II or III breast cancer involving 10 or more nodes were treated with CTCb after six cycles of adjuvant therapy with an anthracycline-containing regimen. Bone marrow (BM) was used as the source hematopoietic stem cell in the first 23 patients and G-CSF-mobilized peripheral blood progenitor cells (PBPC) in the other 17. No therapy-related deaths occurred, but three life-threatening Complications were recorded which resolved: bilateral pulmonary hemorrhage, veno-occlusive disease of the liver and pulmonary thromboembolism. PBPC result in faster hemopoietic reconstitution with significantly lower transfusion requirements. With a median follow-up of 35 months (23-59) actuarial event-free survival for the study patients at 3 years is 72% (CI 95%: 66-81%). Even in patients over 50-60 years, CTCb is a relatively well tolerated regimen which appears, after a median follow-up of nearly 3 years, to decrease relapse frequency as compared with historical series, although a definite role of HDT in the treatment of high-risk primary breast cancer needs confirmation in prospective randomized trials.

Clinical results in 50 multiply transfused patients with severe aplastic anemia treated with bone marrow transplantation or immunosuppressive therapy.

Fifty patients with aplastic anemia (AA) were treated with BMT or immunosuppressive therapy (IST). Twenty-one patients underwent BMT using cyclophosphamide (CY) and 7 Gy total lymphoid irradiation (TLI) and cyclosporin A (CsA) plus methotrexate (MTX). Actuarial survival is 71% at 5.3 years with an incidence of graft failure of 0% and of acute GVHD of 38.9%. Univariate analysis of variables influencing survival showed a trend for a poorer outcome in patients who received > 30 transfusions prior to BMT and in male recipients from female donors. Twenty-nine patients > 40 years of age or without matched siblings received antithymocyte/antilymphocyte globulin (ATG/ALG). Response rate to the first course of treatment was 46.4%. Subsequent courses of IST rescued 33% of patients who relapsed or had not responded. Actuarial survival is 62% at 8.6 years. In our experience both treatment strategies have given encouraging results although overall morbidity is higher in the IST group because 25% of patients are therapy or transfusion-dependent. The role of irradiation in the conditioning regimen of BMT patients, recently challenged, is discussed.

Clinical results of a stringent policy on prophylactic platelet transfusion: non-randomized comparative analysis in 190 bone marrow transplant patients from a single institution.

The threshold for prophylactic platelet transfusion remains controversial. Usually the decision is based on arbitrary numerical criteria. The classical 20 x 10(9)/l trigger could be safely reduced with considerable benefits. Few studies have evaluated the clinical impact of stringent policies. We have performed a retrospective analysis comparing major haemorrhages during hospitalization in 190 patients undergoing BMT in two different periods. In 87 patients transplanted from 1990 to 1991, the 20 x 10(9)/l trigger was used for prophylactic platelet transfusion. In 103 other patients transplanted from 1993 to 1994, we adopted a stringent prophylactic policy: < 10 x 10(9)/l for stable patients and < 20 x 10(9)/l when higher platelet consumption factors were present. In the stringent group, 12 patients presented 13 major haemorrhages and four died from haemorrhage. In the classical group 12 patients presented 14 major haemorrhages and three died from haemorrhage. Platelet consumption factors were present in 12 of 13 haemorrhages in the stringent group and in 12 of 14 in the classical group. By contrast, stable patients presented less haemorrhages (2/14 and 1/13, respectively). A statistically significant reduction in the use of platelet units was observed when comparing both groups: the median of platelet units administered in the first 100 days of transplant was 73 (3-943) and 54 (0-647) in the classical and in the stringent group, respectively (P < 0.01); and the median of platelet units received per day was 0.8 (0.03-30) and 0.5 (0-6.94) (P < 0.01). Our results emphasize the safety of a stringent prophylactic platelet transfusion policy after BMT, reducing the overall use of platelet transfusions. Further studies are necessary to confirm these results and to define optimal transfusion strategies.

Chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation from matched related donors. A case-control study. Spanish Group of Allo-PBT.

We retrospectively compared the incidence and clinical characteristics of cGVHD in 37 allo-PBT recipients transplanted between July 1994 and October 1996 and 37 historical control allo-BMT recipients in a case-control study. All patients received a first unmanipulated transplant, graft from an HLA-identical sibling donor, with CsA-MTX GVHD prophylaxis and survived more than 100 days after transplant. PBT and BMT groups were well matched for age, grade of acute GVHD, male patients grafted from female donors, and phase of disease. The median CD34+ and CD3+ cell numbers infused in the PBT group were 5.2 x 10(6)/kg and 307 x 10(6)/kg, respectively. The median time to an ANC greater than 0.5 x 10(9)/l was 16 days (range 11-22) after PBT and 22 days (range 14-36) after BMT (P < 0.001). The median time to a platelet count greater than 20 x 10(9)/l was 15 days (range 6-43) after PBT and 28 days (range 12-68) after BMT (P < 0.001). Median follow-up was 12.3 months (range 5.4-30.3) and 58.7 months (range 4-122.3), for patients receiving PBT and BMT, respectively. Seventeen out of 37 (46%) PBT recipients, vs nine out of 37 (24%) BM recipients developed cGVHD. Actuarial probability of cGVHD at 1 year was 59% (95% CI, 39-79) in the PBT group vs 27% (95% CI, 12-42) in the BM group (P = 0.01). Cumulative incidence estimate of cGVHD was 51% and 25%, for patients receiving PBT and BMT respectively (P = 0.03). Clinical characteristics of cGVHD and response to therapy were similar in both groups, except for a higher incidence of de novo cGVHD in the PBT group. Our results suggest that as compared with BMT, PBT may result in an increased incidence of cGVHD.

Interferon alpha for chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation.

Interferon alpha (IFN alpha) induces cytogenetic responses in patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT). The purpose of this study was to analyze the therapeutic role of IFN alpha in this setting. The experience of a single institution and the published results on this topic were evaluated. We have included patients who received IFN alpha as a single agent, excluding those patients who received previous or simultaneous donor leukocyte infusions. The outcomes of 11 patients treated in our center and those of 108 previously reported patients have been analyzed. Five out of 11 patients treated in our institution obtained a complete cytogenetic response (CGR). Two patients continue in complete cytogenetic response 3.5 and 8.2 years later, and the qualitative RT-PCR is negative for bcr-abl RNA. The CGR has been transient in one patient, and follow-up is short in the other two. Secondary effects have been acceptable, with myelosuppression as the main toxic effect. Graft-versus-host disease did not occur. The literature review identified 108 patients treated with IFN alpha as sole therapy for relapsed CML. Cytogenetic response and CGR seem to be better in patients with cytogenetic relapse, as compared to patients with hematologic relapse (61% vs. 45% and 45% vs. 28%, respectively). Several patients remained in CGR for more than 5 years. This overview also suggests that CGR is more frequent when IFN alpha is used in patients relapsing after non T-depleted BMT. IFN alpha induces complete cytogenetic response in nearly half of the patients with CML who relapse after allogeneic BMT, with acceptable toxicity. We believe that these results using IFN alpha as a front-line therapy for CML relapsing after BMT warrant a randomized comparison with donor lymphocyte infusions.

Absence of influence of prior treatment with interferon on the outcome of allogeneic bone marrow transplantation for chronic myeloid leukemia.

Timing of transplantation in the chronic phase of chronic myeloid leukemia (CML) and previous treatment with interferon remains controversial. We have tried to discover what influence pretreatment with interferon alpha (IFN-A) has on the results of allogeneic bone marrow transplantation for CML patients treated in a single institution. Fifty-one consecutive patients with chronic phase Ph-positive CML who received an allogeneic bone marrow transplantation from a HLA-identical familial donor were evaluated. Thirty had been treated with IFN-A (IFN+ group) prior to BMT and twenty-one had not (IFN- group). Both groups were homogeneous for clinical characteristics such as age, sex, previous chemotherapy, disease status, and time from diagnosis to transplant. No difference was found in neutrophil and platelet count recovery between the IFN+ and IFN- group. The incidence of acute and chronic GVHD, VOD and severe mucositis was not significantly different. Relapse and both overall survival and DFS were similar for both groups. No adverse effects of prior IFN exposure on the outcome of HLA-identical sibling donor BMT for chronic phase CML patients were found in this study.

Autologous stem cell transplantation (ASCT) for poor prognostic Hodgkin's disease (HD): comparative results with two CBV regimens and importance of disease status at transplant.

Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT in our Department was analyzed retrospectively. Median age was 28 years (28 males and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse) and two had primary refractory disease. The CVB regimen with two different schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300 mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY 7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28 evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2 years, actuarial overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%, with a median follow-up for the surviving patients of 3 years (0.7-7.6). No differences in these survival functions according to the CBV regimen used were observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1 year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of extranodal disease at transplant (P=0.01), and a CR status at transplant (P=0.0006) were associated with a better PFS on univariant analysis. On multivariate analysis, only CR status at transplant remained significant (P=0.05). When patients in second CR at transplant and those in first sensitive relapse were analyzed separately, no differences in clinical characteristics or in treatment received pretransplant were observed; however, PFS was significantly different (P=0.01). In conclusion, CR status at transplant is useful in identifying 'good risk' patients and is necessary to obtain the greatest benefit from ASCT independent of the CBV regimen used.