Samuel Vokurka

The comparative effects of povidone-iodine and normal saline mouthwashes on oral mucositis in patients after high-dose chemotherapy and APBSCT—results of a randomized multicentre study

Antimicrobial solutions are widely used in the nursing care of chemotherapy induced oral mucositis (OM). There is little evidence, however, supporting their use for reducing mucosal damage. In our study, 132 patients were randomized to use normal saline (n=65) or povidone-iodine diluted 1:100 (n=67) mouthwashes for OM prophylaxis and treatment after high-dose chemotherapy comprising BEAM or HD-L-PAM followed by autologous peripheral stem cell transplantation. The study groups were well balanced in respect of age, sex, chemotherapy and the number of CD34+ cells in the graft. No significant difference was found between the groups in respect of OM characteristics, fever of unknown origin (FUO) and other infections. The antimicrobial solution was less tolerable for patients. OM occurred significantly more often in females than in males (86% vs 60%, P=0.0016) and was worse and of longer duration. The mechanical effect of mouthwashes might have a certain importance in FUO prevention. When indicating oral rinses, the patient’s individual preference and tolerance of solutions offered should be considered.

Higher incidence of chemotherapy induced oral mucositis in females: a supplement of multivariate analysis to a randomized multicentre study

Study on the normal saline vs povidone–iodine mouthwashes for oral mucositis (OM) prophylaxis in patients after high-dose chemotherapy comprising bischloroethyl nitrosourea etoposide ara-C melphalan (BEAM) or high-dose melphalan (HD-L-PAM) followed by autologous peripheral stem cell transplantation indicated that females have higher a incidence of OM compared to men, as reported by [Vokurka et al. 13:554–558, (2005)]. The multivariable analysis of larger cohort of 148 patients compliant with the original study protocol confirmed female gender to be an independent risk factor and predictor for OM. The HD-L-PAM (200xa0mg/m2) conditioning regimen revealed to be more toxic compared to BEAM as for incidence of OM grades 3–4 World Health Organization score. Body mass index, age, mouthwash solution used, and CD34+ cell number in the autologous graft were verified not to have an impact on OM incidence in this group of patients.

The effect of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) on oral microbial colonization and pain control compared with other rinsing solutions in patients with oral mucositis after allogeneic stem cells transplantation.

Summary Background Gelclair is an oral lubricating gel used in the management of oral mucositis (OM). We evaluated its efficacy, tolerance and impact on oral cavity microbial colonization in patients with OM after allogeneic hematopoietic stem cells transplantation. Material/Method Gelclair was administered in a group of 22 patients with active OM. A control group of 15 patients used other rinsing solutions (chlorhexidine, benzydamine, salvia). Tests with oral cavity swabs for microbiology analysis were performed once a week. Results The characteristics of OM in both groups were comparable, and rinsing solutions had satisfactory tolerability. There was no difference in the median improvement of oral intake and OM-related pain relief, which was assessed mostly as “slight effect”. In the Gelclair group, the effect duration was longer (median 3 [0–5] vs. 1 [0–3] hours, p=0.001). There was significant increase of Enterococcus faecalis and Candida sp. colonization of the oral cavity over the course of the hospitalization and significantly reduced incidence of such colonization in patients with OM in the Gelclair group: 1/22 (5%) vs. 6/15 (40%), p=0.01. In vitro tests showed inhibited growth of Enterococcus faecalis and Candida sp. colonies within the area of the Gelclair application. Conclusions Gelclair may be individually helpful in the management of OM and pain in patients after allogeneic stem cells transplantation. Its use did not lead to worsened oral bacterial and yeast colonization and probably even helped to protect mucosa from Enterococcus and Candida sp. Further studies based on larger cohorts are needed.

The risk factors for oral mucositis and the effect of cryotherapy in patients after the BEAM and HD-l-PAM 200 mg/m2 autologous hematopoietic stem cell transplantation

PURPOSEnOral mucositis (OM) still represents a significant complication of hematopoietic stem cell transplantations (HSCT). Observational studies focusing on risk factor definitions are still warranted.nnnMETHODnA total of 126 patients participated in this observational study after autologous HSCT with the BEAM and HD-l-PAM 200mg/m(2) conditioning regimens. Basic clinical and laboratory variables and their impact on OM were assessed.nnnRESULTSnAge, gender, body mass index, and baseline absolute neutrophil counts were not shown to have any negative impact on OM development. The multivariate analysis revealed oral cryotherapy non-provision as being the most significant predictor for OM incidence (p < 0.0001), followed by BEAM conditioning regimen (p = 0.007), OM in a patients history (p = 0.002) and lower number of days since the last chemotherapy (p = 0.025). The cryotherapy was remarkably effective both in the single high-dose melphalan 200mg/m(2) conditioning regimen (18% OM in cryotherapy vs. 68% without it, p<0.0001) and in the multidrug BEAM (melphalan 140mg/m(2)) regimen (38% vs. 86%, p=0.006).nnnCONCLUSIONnOral cryotherapy should be implemented into supportive care management in patients treated with high-dose melphalan short-infusion chemotherapy. Large and well-designed randomized trials are necessary to obtain more significant and reliable results and understanding regarding OM risk factors.

Antimicrobial chlorhexidine/silver sulfadiazine-coated central venous catheters versus those uncoated in patients undergoing allogeneic stem cell transplantation

IntroductionOnly a minimum is known about clinical effect of antimicrobial-coated central venous catheters (CVC) in stem cell transplantation settings, where CVC-related infections impose major threat to severely immunocompromised patients.Materials and methodsIn this prospective, non-sponsored and nonrandomized study, there were 49 uncoated multi-lumen and non-tunneled CVCs and 58 antimicrobial chlorhexidine/silver sulfadiazine-coated CVCs inserted in allogeneic stem cell transplanted patients to facilitate treatment during conditioning and pre-engraftment phase (<30days after transplantation).Results and discussionNo significant differences were found between the two groups with respect to gender, age, intensity of pretransplant chemotherapy conditioning, duration of leucopenia, number of days with inserted CVC, number of CVC occlusive dressing changes performed per patient, and number of non-CVC-related infections. In the antimicrobial coated CVC group, there were observed less median days with fever [2 (0–18) vs. 4 (0–16), p = 0,17], fever incidence (67% vs. 77.5%, p = 0.28), and less days with fever per 1,000 catheter-days (108 vs. 147, p = 0.001), less patients with positive CVC blood cultures (36% vs. 45%, p = 0.05), repeatedly positive CVC blood cultures (8.6% vs. 26%, p = 0,018), less positive CVC blood cultures per 1,000 catheter-days (14 vs. 29, p = 0.005), and less positive CVC tip cultures (17.3% vs. 34.6%, p = 0.065) observed.ConclusionLower number of patients with fever, days with fever, and lower number of patients with positive and repeatedly positive CVC blood cultures indicates less intensive antibiotic and antipyretic treatment probably needed in neutropenic allo-transplanted patients with indwelling antimicrobial-coated CVCs. Real impact on antibiotic consumption should be verified in large randomized study.

The availability of HEPA-filtered rooms and the incidence of pneumonia in patients after haematopoietic stem cell transplantation (HSCT): results from a prospective, multicentre, eastern European study

AIMS AND OBJECTIVESnTo establish the availability of High Efficiency Particulate Air (HEPA)- and nonHEPA-filtered rooms in eastern European transplant centres and to investigate the impact on incidence of pneumonia and mortality after haematopoietic stem cell transplantation (HSCT).nnnBACKGROUNDnBarrier nursing in HEPA-filtered rooms is generally recommended for patients undergoing HSCT. There are only limited data on the availability of HEPA-filtered rooms and the impact on incidence of pneumonia and mortality.nnnDESIGNnA prospective, observational, international study.nnnMETHODSnMonitoring cards were distributed within the East Forum EBMT-Nurses Group cooperating centres, and 689 consecutive patients were registered in 1/2010-6/2012. Patients were monitored for 100 days post-transplant.nnnRESULTSnIn patients undergoing autologous HSCT, pneumonia developed in 14/400 (3·5%) and was the cause of death in 2/14 (14%) of patients. There was no significant difference in mortality between HEPA-filtered and nonHEPA-filtered groups (4·5% vs. 4·9%, respectively). 239/400 (59%) transplantations were performed in single-bed rooms [190/239 (79%) HEPA-filtered] and 161 (41%) in two-bed rooms [28/161 (17%) HEPA-filtered]. In allogeneic transplantation, pneumonia developed in 24/289 (8·3%) and was the cause of death in 11/24 (45%) of patients. There was no significant difference in mortality between HEPA-filtered and non-HEPA-filtered groups (14% vs. 17%, respectively). 281/289 (97%) of allogeneic transplantations were performed in single-bed rooms [254/281 (90%) HEPA-filtered], and pneumonia was more frequent in patients on corticosteroids and in rooms without HEPA.nnnCONCLUSIONnThe incidence of pneumonia in the autologous transplantation setting is low. More pneumonia was observed in the allogeneic HSCT group, especially in patients on corticosteroids. There was a trend towards a lower incidence of pneumonia in allogeneic HSCT patients treated in HEPA-filtered rooms.nnnRELEVANCE TO CLINICAL PRACTICEnAutologous HSCT transplantation may safely be performed without HEPA filtration. HEPA filtration might be preferable in patients undergoing allogeneic transplantation.

The translocation t(2;11)(p21;q23) without MLL gene rearrangement—a possible marker of good prognosis in myelodysplastic syndrome patients

The translocation t(2;11)(p21;q23) is associated with de novo myelodysplastic syndromes (MDS) and has an overall frequency of approximately 1%. The outcome of MDS patients with this translocation is not clear until now, because most of the clinical data addressing the t(2;11)(p21;q23) has been collected without investigating the status of the mixed lineage leukemia (MLL) gene. In this report, we present seven new patients with MDS diagnosis and the t(2;11)(p21;q23) in bone marrow cells; all of them without MLL gene rearrangement. They were found in two databases consisting of 1185 patients of two Czech institutions. These patients tended to be younger and showed a strong male predominance. A cytological and histological assessment of bone marrow at diagnosis revealed only mild MDS with marked dysplasia in megakaryopoiesis. Similar to other primary abnormalities in MDS (e.g. deletion of 11q), the t(2;11)(p21;q23) was frequently associated with deletion of 5q. Our results stress the common clinicopathological features of this entity and indicate that the t(2;11)(p21;q23) may be associated with a good prognosis for MDS patients (median survival 72u2009months). Copyright

Oropharyngeal mucositis pain treatment with transdermal buprenorphine in patients after allogeneic stem cell transplantation.

The two key points about this case are 1) effective treatment of her neuropathy with topical menthol allowed continued tumoricidal life-prolonging treatment and 2) when treatment with topical menthol was continued during chemotherapy, the peripheral neuropathy did not deteriorate. The rationale for using topical menthol was based on our findings indicating that the TRPM8 receptor may be a potential target for the treatment of neuropathic pain. A prominent analgesic effect of cooling compounds that activate TRPM8 was demonstrated in a rodent model of neuropathic pain. An increase in TRPM8 receptor expression occurs in some sensory neurons after nerve injury, possibly contributing to enhanced analgesic effects to cooling agents. Previous work from our group has shown that topical menthol has an analgesic effect in chemotherapy-induced neuropathy, although the effect of the challenge of additional chemotherapy was not assessed. This case uniquely demonstrates that topical menthol may prevent recurrence of neuropathy. Treatment-related neuropathies can limit successful disease control in cancer care. This is relevant to several classes of chemotherapy drugs, and often, treatment even with strong opioids and adjuvant analgesics (such as amitriptyline or gabapentin) has limited efficacy and other side effects. We have demonstrated significant therapeutic response using topical menthol to counteract carboplatin-induced neuropathic pain, which previously had prevented further delivery of platinum or taxane-based chemotherapy. Of note, it appears that continued application during chemotherapy prevented neuropathy worsening, and there were no adverse effects. This case demonstrates the value of close collaboration between translational research and the clinical setting to enable effective chemotherapy delivery, prolonged survival, and good symptom control for cancer patients.

Successful Peripheral Blood Stem Cells Collection in Imatinib Pretreated and Nilotinib-Treated Chronic Myeloid Leukemia Patient

We report a case of a successful mobilization and harvest of the peripheral blood stem cells (PBSCs) in imatinib-pretreated and nilotinib treated 52-year-old woman diagnosed with Philadelphia chromosome-positive and BCR-ABL (b2a2) positive chronic phase CML in 2/2002. She failed interferon-alfa and imatinib treatment. She achieved her first complete molecular remission after 16 months of nilotinib treatment and later on was mobilized with filgrastim at a dose of 10u2009ug/kg/day applied subcutaneously once daily. The total number of 2.98 × 106 CD34+u2009cells/kg was harvested on the fourth day of the mobilization. The autologous graft of the stem cells was cryopreserved and tested for the residual disease: the FISH revealed negative results and the RT-PCR was positive (BCR-ABL/ABL ratio 0,0017 in RQ-PCR). To our knowledge, this is the first report of successful PBSC harvest in a patient significantly pretreated with imatinib and nilotinib.