Immunoablation and autologous hematopoietic stem cell transplantation in the treatment of new-onset type 1 diabetes mellitus: long-term observations.

The activity of the autoimmune mechanism underlying type 1 diabetes mellitus (T1DM) can be suppressed when immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) are applied early in the course of the disease. We report here a single centre experience with this treatment modality. Twenty-four patients underwent a AHSCT preceded by immunoablative conditioning with high-dose cyclophosphamide and anti-thymocyte globulin. During the 52-month median time of follow-up 20 out of 23 patients (87%) remained for at least 9.5 months without the use of exogenous insulin. The median time of T1DM remission for these patients was 31 months (range of 9.5-80 months). Among the patients available for follow-up (n=20), four remain insulin free (for 80, 61, 42 and 34 months). The average glycated hemoglobin (HbA1c) concentrations were 10.9% at diagnosis, 5.9% at 1 year, 6.4% at 2 years, 6.8% at 3 years and 7.1% at 4 years after AHSCT. No severe complications of diabetes were seen, however one of the patients died of pseudomonas sepsis in the course of neutropenia after AHSCT. AHSCT leads to a remission of T1DM with good glycemic control in the vast majority of patients, with the period of remission lasting over 5 years in some patients.

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients--Report of the Polish Myeloma Group.

UNLABELLED: The aim of the multi-centre retrospective study was to evaluate the efficacy and safety of lenalidomide (LEN) therapy in patients with resistant or relapsed multiple myeloma (MM) as well as in patients with stable disease (LEN used due to neurological complications). The primary endpoint of this study was an overall response rate (ORR). The secondary endpoints were as follows: time to progression (TTP), overall survival (OS) and the safety of drug use. Data were collected in 19 centres of the Polish Multiple Myeloma Study Group. The study group consisted of 306 subjects: 153 females and 153 males. In 115 patients (38.8%, group A), a resistant myeloma was diagnosed; in 135 (44.1%, group B) a relapse, and in 56 (18.3%, group C) a stable disease were stated. In 92.8% of patients, LEN+DEX combination was used; in remaining group, LEN monotherapy or a combination therapy LEN+bortezomib or LEN+bendamustine and other were used. In the entire study group, ORR was 75.5% (including 12.4% patients achieving complete remission [CR] or stringent CR [sCR]). Median time to progression (TTP) was 20 months. Median overall survival (OS) was 33.3 months. The regression model for "treatment response" was on the borderline of statistical significance (p=0.07), however the number of LEN treatment cycles ≥ 6 (R(2)=17.2%), baseline LDH level (R(2)=1.1%) and no ASCT use (R(2)=1.7%) where the factors most affecting treatment response achievement. The regression model for dependant variable--"overall survival"--was statistically significant (p=0.0000004). Factors with the most impact on OS were as follows: number of LEN cycles treatment ≥ 6 (R(2)=16.7%), treatment response achievement (R(2)=6.9%), ß-2-microglobulin (ß-2-M) level (R(2)=4.8%), renal function (R(2)=3.0%) and lack of 3/4 grade adverse events (R(2)=1.4%). SUMMARY: LEN is an effective and safe therapeutic option, even in intensively treated resistant and relapsed MM patients, as well as in patients with stable disease and previous treatment-induced neurological complications. In particular, the number of LEN treatment cycles ≥ 6 was the factor which affected treatment response achievement the most, together with an important impact on OS.

Correlates of unrecognized acute myocardial infarction detected via perfusion imaging.

Research using the electrocardiogram (ECG) indicates that about 1/3 of acute myocardial infarctions (AMIs) are unrecognized. To date, no studies of unrecognized AMIs have employed perfusion imaging, although it is more sensitive than the ECG and provides more information about infarct characteristics, such as size and location. In this study, 82 of 258 consecutive patients (31.8%) undergoing exercise testing with technetium-99m sestamibi perfusion imaging had fixed, nonartifactual perfusion defects, suggesting AMI. These patients were interviewed regarding their recognition of AMI; 27 patients (32.9%) had unrecognized AMI. Unrecognized AMI was significantly associated with (1) smaller infarcts, (2) infarcts not in the apical or septal regions, (3) diabetes mellitus, (4) lack of angina, (5) a negative family history for cardiac disease, and (6) being African-American. Many of these variables were significantly intercorrelated, and in multivariate analysis, unrecognized AMI remained significantly predicted by a smaller infarct and lack of angina. This study suggests that the incidence of unrecognized AMI detected via perfusion imaging on a clinic population is similar to that detected via electrocardiographic studies on community samples. This study also replicates prior findings of the medical history and demographic correlates of unrecognized AMI, and indicates that infarct size and location are also associated with unrecognized AMI.

Silent versus symptomatic myocardial ischemia: the role of psychological and medical factors.

This study examined the relationship of psychological, cardiac, and general medical history factors to asymptomatic (silent) versus symptomatic myocardial ischemia among 102 patients who underwent treadmill exercise testing and had perfusion imaging indicative of ischemia. During exercise, 68 patients exhibited silent ischemia, and 34 experienced chest pain. Patients with silent ischemia rated higher than symptomatic patients on anger control, externally oriented thinking, and somatosensory amplification, but did not differ on depression or global alexithymia. Anger control and externally oriented thinking remained independent correlates in multivariate analysis, controlling for demographic and cardiac factors. Groups did not differ on general medical or cardiac variables. Thus, this study suggests that affective and cognitive factors, but not biomedical factors, are associated with silent, as opposed to symptomatic, ischemia during exercise testing.

Decreased health care use among patients with silent myocardial ischemia: support for a generalized rather than cardiac-specific silence.

OBJECTIVE: The absence of angina among patients with silent myocardial ischemia (SMI) may be a cardiac phenomenon or may reflect a generalized lack of bodily awareness and symptom reporting. We tested the hypothesis that the silence is generalized, and, therefore, that patients with SMI would make fewer health care visits for noncardiac/chest-pain problems than patients with symptomatic ischemia. METHODS: We counted all out-patient visits to our medical system for the prior 18 months for 95 patients who demonstrated ischemia during treadmill exercise testing and subsequent nuclear scanning: 62 of the patients had SMI during exercise, and 33 of the patients had symptomatic ischemia. RESULTS: Patients with SMI made were significantly less likely to have sought emergency care or primary care and had significantly fewer primary care visits than patients with symptomatic ischemia. Group differences remained after controlling for demographics and health status variables. The two groups did not differ on utilization of specialty care. CONCLUSION: The reduced use of emergency and primary care among patients with SMI suggests that they have a generalized rather than cardiac-specific reduction in somatic awareness and/or symptom reporting.

Evaluation of relative anti-myeloma activity of high-dose melphalan followed by the first peripheral blood stem cell transplantation, as compared with the second transplantation, and to VAD chemotherapy.

Current treatment in multiple myeloma consists of three courses of chemotherapy in low doses with subsequent hematopoietic stem cell mobilization to the peripheral blood using high-dose cyclophosphamide, collection and conditioning with high-dose chemotherapy (melphalan) followed by retransplantation of autologous peripheral blood stem cells (PBSCT). Only a few studies compare the effects of different phases of therapy on parameters, such as monoclonal immunoglobulin level and the presence of malignant CD38(+) and CD56(+) cells in blood and marrow. The aim of this study was to compare the effects of these two major phases of treatment (conventional and high dose) in the same patients, and furthermore, to compare the effects of the second course of high-dose therapy followed by PBSCT with the effects of the first one. Fifteen patients were included in the study. On average, conventional chemotherapy only slightly reduced the values of all disease markers. In contrast, high-dose therapy resulted in a dramatic effect, rapidly normalizing the values of all parameters. The effects of second PBSCT were only modest compared to the first. These data suggest that high-dose therapy is an efficient method to reduce tumor load in multiple myeloma. Conventional-dose chemotherapy may be simply a waste of time for some patients and may be either omitted or administered after high-dose therapy to consolidate remission.

Triple transplantation of autologous peripheral blood stem cells each time following conditioning with 100 mg/m2 of melphalan for multiple myeloma patients in poor performance status.

Approximately one third of multiple myeloma patients (below 60 years) are diagnosed either in advanced disease or with significant comorbidities. Many other patients referred to transplant centers have already been heavily pretreated with multiple courses of various conventional chemotherapies. These patients are frequently in bad or even grave clinical condition; they are unlikely to survive standard high-dose melphalan (200 mg/m(3)) chemotherapy and autologous hematopoietic stem cell transplantation. Palumbo et al reported a protocol for elderly patients that utilized reduced conditioning (melphalan 100 mg/m(2) three times at 2-month intervals, each time supported by autologous hematopoietic rescue). We have used this protocol as a start to develop a method to induce a remission in the aforementioned subgroup of myeloma patients. Patients with stage III disease and WHO performance status 2 or higher are treated with one or two cycles of cyclophosphamide (2 to 4 g/m(2)) and undergo peripheral blood stem cells collection. Subsequently, they are treated with three to four doses of melphalan (100 mg/m(2)) at 8- to 12-weeks intervals each time supported by infusion of peripheral blood stem cells. To date 13 patients have been entered into the protocol. With one exception of transiently stable disease, the remaining patients obtained at least partial remission and three, complete remission. The compliance was good and better with each subsequent course. For half of the patients the problem was a short duration of response. This method when developed may offer a new treatment alternative for a subgroup of high-risk multiple myeloma patients.

High-dose melphalan and autologous hematopoietic stem cell transplantation in primary amyloidosis: single-center results.

BACKGROUND: Systemic immunoglobulin light-chain amyloidosis (AL) is a plasma cell dyscrasia resulting in multisystem organ failure and death. Autologous hematopoietic stem-cell transplantation (ASCT) has been widely used to treat patients with AL. However, treatment-related mortality remains high and reported series are subject to selection bias. METHODS: To define the role of patient selection in stem cell transplantation, we evaluated 24 consecutive AL patients transplanted at our center. RESULTS: Complete hematologic response was achieved in all 20 patients surviving >100 days posttransplantation. The 1-year overall survival (OS) rate after ASCT was 78.5%. The 5- and 10-year progression-free and OS rates were 57% and 47%, respectively. Treatment-related deaths owing to cardiovascular problems occurred in 16% of cases. CONCLUSION: ASCT for AL amyloidosis can be safely performed in experienced transplantation centers, and increased risk is associated mainly with cardiovascular system involvement.

Independence of exogenous insulin following immunoablation and stem cell reconstitution in newly diagnosed diabetes type I.

Type I diabetes mellitus is a metabolic disease caused by chronic immune attack against the insulin-producing cells of the pancreas. It has recently been shown that the clinical course of this disease can be interrupted by immune ablation and PBSCT. In this report, we describe our experience with this treatment modality in a series of eight cases. Patients with newly diagnosed type I diabetes were received treatment consisting of two to three plasmaphereses, hematopoietic stem cell mobilization with CY and G-CSF, collection of at least 3 × 10(6) per kg of CD34+ cells, and conditioning with CY and anti-thymocyte globulin followed by stem cell infusion. All patients became independent of exogenous insulin after the transplantation. One patient resumed low-dose insulin 7 months after transplantation. Six out of eight patients were given acarbose for better glycemic control after transplantation. All patients exhibited good glycemic control: the average HbA1c concentrations were 12.3% at diagnosis, and 5.6 and 6.2% at 3 and 6 months after transplantation, respectively. We conclude that at least temporary independence of exogenous insulin can be achieved in type I diabetes patients following immunoablation and reconstitution of the immune system with autologous PBSCs.

The relationship of alexithymia to subjective and biomedical measures of disease.

Although alexithymia is found in patients with various somatic disorders, it is unclear whether alexithymia is related to organic disease, or just to illness behavior. In 2 studies of patients, the authors related alexithymia (using the Toronto Alexithymia Scale-20 for assessment) to both subjective reports and biomedical measures of disease. In Study I, alexithymia was correlated with symptoms, but not CD4 counts, among adults who had tested positive for the human immunodeficiency virus. In Study 2, alexithymia was associated with the presence or absence of chest pain during exercise testing, but not with ischemic heart disease. These studies suggest that alexithymia, especially difficulty identifying and/or describing feelings, is related to increased illness behavior, but alexithymia may not be related to the presence or severity of organic disease.

Psychosocial factors related to noncardiac chest pain during treadmill exercise.

The authors examined historical, concurrent, and potentially secondary psychosocial problems related to noncardiac chest pain during exercise. The patients reporting chest pain during treadmill testing but who lacked cardiac ischemia (determined via nuclear scanning) were compared with the patients having both ischemia and chest pain, and with patients having neither ischemia nor chest pain. The noncardiac chest pain patients had the highest levels of 1) parental divorce and personal psychiatric treatment; 2) current depression, somatic awareness, and anger control; and 3) negative attitudes toward the health care system. The findings suggest that psychosocial problems predate, coexist with, and may result from noncardiac chest pain.

Screening for somatizing patients in the pulmonary subspecialty clinic.

Somatizing patients present a history of vague, unexplained medical symptoms. This study compared somatizing patients with pulmonary control subjects by using the Diagnostic Interview Schedule (DIS-III-R), the Illness Attitude Scales (IAS), and the Minnesota Multiphasic Personality Inventory (MMPI-2). The groups differed in the number of somatization symptoms reported and in the frequency of somatization disorder diagnoses when the screening criteria were used. The somatizing group obtained higher scores on the bodily preoccupation and hypochondriacal beliefs subscales of the IAS; no differences were found on the MMPI-2. These findings indicate that the DSM-III-R somatization screening items can be useful for detecting somatization when patients present with unexplained respiratory complaints.