Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of New Drugs

Background & Aims. The present retrospective single-center study analysed the impact of high-dose chemotherapy with melphalan with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) on survival in multiple myeloma (MM) in the era of new induction regimens. Materials & Methods. The clinical trial included 133 MM patients aged from 31.2 to 78.2 years (the median age was 55.3 years). There were 66 female and 67 male patients. Bortezomib-based regimens as first-line treatment were administered in 133 MM patients, 74 of them received high-dose chemotherapy with melphalan and either single (n = 25), or double (n = 49) auto-HSCT as consolidation therapy in the period from 2006 to 2016. Results. The overall 5-year survival (OS) rates were 86.5 % for the auto-HSCT treated group vs. 72.9 % for the non-auto-HSCT treated group (p = 0.03); 5-year progression-free survival (PFS) rates were 64.9 vs. 39 % for the auto-HSCT and non-auto-HSCT treated groups, respectively (p = 0.0016). MM relapse/progression occurred more frequently in the non-auto-HSCT treated patients (52.5 vs. 28.4 %; p = 0.0016). In multivariate analysis the age above 60 was determined as prognostic factor of lower PFS and increase in relapse/progression rate (p = 0.004 and p = 0.04, respectively). The variant of monoclonal protein (Bence-Jones myeloma) was determined as prognostic factor of higher OS and decrease in relapse/progression rate (p = 0.02 and p = 0.04, respectively). Complete nonresponsiveness to induction therapy has proved to be an independent predictor of both poor OS and PFS (p = 0.04 and p = 0.041, respectively). 2-year bortezomib-based maintenance therapy following the auto-HSCT treatment resulted in a statistically significant improvement in 5-year PFS (67.4 vs. 60.7 %; p = 0.03) and a decrease in relapse/progression frequency (26.1 vs. 32.1 %; p = 0.05). Conclusion. High-dose chemotherapy with melphalan with subsequent auto-HSCT is an effective MM treatment strategy, and a subsequent long-term maintenance therapy results in a PFS improvement and a decrease in relapse/progression frequency

Comparative Study of Mycophenolate Mofetil and Methotrexate in Graft-Versus-Host Disease Prophylaxis in Adult Recipients of Related and Unrelated Allo-HSCT

Background. Although the use of methotrexate (MTX) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) was compared in a large number of studies, the published results are contradictory. This fact provides ground for the present retrospective single-center trial comparing these two approaches in GVHD prophylaxis. Materials & Methods. The present study included 294 allo-HSC recipients with MTX prophylaxis and 172 allo-HSC recipients with MMF prophylaxis. 36 % of patients underwent matched related donor transplantation, and 64 % of patients received matched unrelated donor transplantation. Results. Univariate and multivariate analyses showed that probability of acute grade 2–4 GVHD is 36 % vs. 39 % (hazard ratio [HR] 1.297; 95% confidence interval [95% CI] 0.931–1.795; p = 0.122), grade 3–4 GVHD was 21 % vs. 25 % (HR 1.472; 95% CI 0.951–2.256; p = 0.05), and probability of chronic GVHD was 52 % vs. 55 % (HR 0.978; 95% CI 0.951–1.406; p = 0.91). In the MTX and MMF groups there were no significant differences in transplantation mortality (HR 1.173; 95% CI 0.797–1.708; p = 0.43), relapse incidence (HR 1.034; 95% CI 0.743–1.428; p = 0.84), overall survival (HR 1.087; 95% CI 0.825–1.433; p = 0.55), event-free survival (HR 1.108; 95% CI 0.854–1.437; p = 0.43), disease and GVHD free survival (HR 1.065; 95% CI 0.845–1.343; p = 0.59). Engraftment occurred earlier when MMF was used (p = 0.035). Administration of MMF instead of MTX was associated with lower probability of toxic grade 3–4 hepatitis (7 % vs. 31 %; p < 0.0001) and grade 3–4 mucositis (23 % vs. 45 %; p = 0.0002). Conclusion. The efficacy of GVHD prophylaxis using MMF is comparable with that of MTX, but MMF is associated with a better safety profile due to reduced incidence of severe liver toxicity and mucositis

Elevated temperature lasing from injection microdisk lasers on silicon

The combination of high operation temperatures and small diode lasers directly grown on silicon substrates is essential for their application in future photonic integrated circuits. In this letter, results are presented for quantum dot III–V-on-Si microdisk diode lasers tested at elevated temperatures. To the best of our knowledge, we have demonstrated the first uncooled microlasers with diameter of 30 µm capable of operating in the continuous wave regime at 60 °C. In the lasing regime, the emission spectra contain one very intense line with a full-width at half-maximum of 30 pm; the side mode suppression ratio reaches 18 dB. Because of self-heating, the actual temperature of the active region is close to 100 °C. Under pulsed excitation, the maximal lasing temperature is 110 °C

Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression

Aim. To estimate the efficacy of chemotherapy in acute leukemia patients resistant to previous standard treatment according to the series measurement of WT1 expression. Materials & Methods. The series measurement of WT1 expression formed the basis of the efficacy estimation of induction chemotherapy in 31 patients (15 men and 16 women aged from 3 months to 68 years; the median age was 28 years) with prognostically unfavourable variants of acute myeloid (AML) and lymphoblastic leukemia (ALL) (23 AML and 8 ALL patients). The WT1 gene expression was measured at baseline and 2–3 weeks after the treatment by the quantitative real-time PCR. The threshold level for detection was 250 copies of WT1/104 copies of ABL. The cytogenetic profile of leukemia cells was assessed by standard cytogenetics and FISH. Results. The baseline expression level of WT1 varied from 305 to 58,569 copies/104 copies of ABL. The expected reduction of WT1 expression after the first induction chemotherapy treatment was reported in 22/23 (96 %) AML patients and in 6/8 (75 %) ALL patients. According to our results WT1 expression reached the threshold in 13/31 (42 %) patients, including 9 AML patients and 4 ALL patients. After 11/31 (35 %) patients received the second course of treatment, WT1 expression level became normal in 8 cases (5 ALL and 3 AML patients). Despite high dose chemotherapy, HSCT and such agents as blinatumomab and gemtuzumab, an unfavourable outcome was observed in 18/31 (58 %) patients including 6 patients with complex karyotype (CK+) and 2 patients with monosomal karyotype (MK+). Once the MK+ and CK+ combination was observed, in another case the MK+ was combined with the prognostically unfavourable inv(3)(q21q26) inversion. Conclusion. Our results show that the molecular monitoring should be included as part of treatment of the prognostically unfavourable acute leukemia. The WT1 gene was shown to be the most appropriate marker. WT1 expression was shown to correlate with the common fusion genes allowing to estimate the blast cell count at the molecular level

Localization of the spectral expansions associated with the partial differential operators

In this paper we discuss precise conditions of the summability and localization of the spectral expansions associated with various partial differential operators. In this we study the problems in the spaces of both smooth functions and singular distributions. We study spectral expansions of the distributions with the compact support and classify the distributions with the Sobolev spaces. All theorems are formulated in terms of the smoothness and degree of the regularizations

InAs/GaAs Quantum Dot Microlasers Formed on Silicon Using Monolithic and Hybrid Integration Methods

An InAs/InGaAs quantum dot laser with a heterostructure epitaxially grown on a silicon substrate was used to fabricate injection microdisk lasers of different diameters (15–31 µm). A post-growth process includes photolithography and deep dry etching. No surface protection/passivation is applied. The microlasers are capable of operating heatsink-free in a continuous-wave regime at room and elevated temperatures. A record-low threshold current density of 0.36 kA/cm2 was achieved in 31 µm diameter microdisks operating uncooled. In microlasers with a diameter of 15 µm, the minimum threshold current density was found to be 0.68 kA/cm2. Thermal resistance of microdisk lasers monolithically grown on silicon agrees well with that of microdisks on GaAs substrates. The ageing test performed for microdisk lasers on silicon during 1000 h at a constant current revealed that the output power dropped by only ~9%. A preliminary estimate of the lifetime for quantum-dot (QD) microlasers on silicon (defined by a double drop of the power) is 83,000 h. Quantum dot microdisk lasers made of a heterostructure grown on GaAs were transferred onto a silicon wafer using indium bonding. Microlasers have a joint electrical contact over a residual n+ GaAs substrate, whereas their individual addressing is achieved by placing them down on a p-contact to separate contact pads. These microdisks hybridly integrated to silicon laser at room temperature in a continuous-wave mode. No effect of non-native substrate on device characteristics was found