Cryptococcus laurentii diarrhea post hematopoietic stem cell transplant.

We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patient's response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient.

Hodgkin's Lymphoma - evaluation of patients submitted to Autologous transplantation of hematopoietic cells in the Hematology Service of the Hospital Walter Cantídio - Fortaleza, Brazil / Linfoma de Hodgkin - avaliação dos pacientes submetidos a transplante autólogo de células hematopoéticas no Serviço de Hematologia do HUWC

SUMMARY The Autologous HSCT is an important alternative for refractory or recurrent HL patients in terms of survival and improved quality of life. This study analyzes the results of autologous BMT performed in HL patients in the Transplant Unit of the HUWC/ HEMOCE (Fortaleza - CE, Brazil). Fifty-two transplanted patients were studied from January 2009 to October 2015, among them, 30 men and 22 women, mean age of 28.2 years. All of them received GCS-F during the mobilization, in some cases associated with Vinorelbine or Plerixafor, with CD34 collection averaging 4.8 CD34/kg. The conditioning was performed with BEAC, NEAM or BEAM and the grafting with an average of 10 days. The evaluation on D + 100 showed: CR - 42 (82.7%), PR - 08 (13.5%) and 02 (3.8%) deaths, three and six days after cell infusion. After the D+100, 08 patients in CR showed HL recurrence from 06 to 36 months; 03 died and 05 are being treated with brentuximab; among the 08 patients in PR, 01 died due to HL activity, 04 months after BMT and 07 patients are undergoing treatment. The final evaluation of HL transplant patients showed an OS of 88.5% and a DFS of 61.5% in 6 years, with OS of the chemosensitive patients of 81% and of the chemoresistant ones, of 72.6%. It is possible to conclude that the Autologous HSCT has shown to be an excellent rescue therapy regarding tolerance, as well as the overall survival.

RESUMO O TCTH autólogo é uma importante alternativa para os pacientes de LH refratários ou recidivados, em termos de sobrevida e melhora da qualidade de vida. O presente trabalho analisa os resultados do TMO autólogo realizado em pacientes de LH na Unidade de Transplante do SH do HUWC/HEMOCE. Foram estudados 52 pacientes submetidos ao TMO de janeiro de 2009 a outubro de 2015, sendo 30 homens e 22 mulheres, média de idade de 28,2 anos. Todos receberam GCS-F na mobilização, em alguns casos associados a Vinorelbine ou a Plerixafor e coleta de CD34 com média de 4,8CD34/kilo. O condicionamento foi realizado com BEAC, NEAM ou BEAM e a enxertia com média de 10 dias. A avaliação no D+100 mostrou: RC – 42 (82,7%), RP – 08 (13,5%) e 02 (3,8%) óbitos ocorridos 3 e 6 dias após a infusão das células. Após o D+100, 08 pacientes em RC apresentaram recidiva do LH entre 6 e 36 meses; 3 foram a óbito e 5 estão em tratamento com brentuximabe; os 8 pacientes em RP, 1 faleceu por atividade do LH, 4 meses após o TMO e 7 estão em tratamento. A avaliação final dos pacientes de LH transplantados mostrou uma SG de 88,5% e SLD de 61,5% em 6 anos, SG dos pacientes quimiossensiveis de 81% e dos quimioresistentes de 72,6%. É possível concluir que o TCTH Autólogo se coloca como excelente terapia de resgate em relação à tolerância, bem como na sobrevida global.

Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation.

Donor lymphocyte infusion (DLI), a standard relapse treatment after allogeneic stem cell transplantation (AlloSCT), has limited efficacy and often triggers GVHD. We hypothesized that after AlloSCT tumor-infiltrating donor lymphocytes could be costimulated ex vivo to preferentially activate/expand antitumor effectors. We tested the feasibility and safety of costimulated, tumor-derived donor lymphocyte (TDL) infusion in a phase 1 trial. Tumor was resected from 8 patients with B-cell malignancy progression post-AlloSCT; tumor cell suspensions were costimulated with anti-CD3/anti-CD28 Ab-coated magnetic beads and cultured to generate TDL products for each patient. Costimulation yielded increased proportions of T-bet(+)FoxP3(-) type 1 effector donor T cells. A median of 2.04 × 10(7) TDL/kg was infused; TDLs were well tolerated, notably without GVHD. Two transient positron emission tomography (PET) responses and 2 mixed responses were observed in these refractory tumors. TDL are a feasible, tolerable, and novel donor cell therapy alternative for relapse after AlloSCT.

Salvage therapy in Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) is a commonly cured malignancy. Unfortunately, patients who are refractory to or relapse after first-line treatment pose a significant therapeutic challenge. There is evidence that these patients are best treated with an approach involving salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT). This approach may result in cure, with better results in patients with low-risk relapse. In patients with high-risk relapse and refractory disease, HDCT/ASCT is rarely curative. More aggressive transplant approaches have shown promising results in this group and are currently under active investigation. For those relapsing after HDCT/ASCT, there exists a range of therapeutic options, including further salvage chemotherapy, reduced-intensity allogeneic transplantation, monoclonal antibody therapy, and novel agents. All patients in this category should be considered for enrollment in clinical trials. This review discusses the evidence behind the current practice in patients with relapsed or refractory HL. Specifically, the efficacy of various salvage chemotherapy regimens, the risk factors influencing outcome with HDCT/ASCT, and the results with alternative transplant approaches, monoclonal antibody therapies, and novel agents are addressed. We conclude by providing our approach to these patients, with the hope that this will serve as a framework for the practicing oncologist.

Sclerodermatous graft-versus-host disease: clinical spectrum and therapeutic challenges.

Sclerodermatous graft-versus-host disease (GVHD) is a rare complication of bone marrow transplantation. While GVHD is often associated with the beneficial graft vs. tumour effect, it also contributes towards significant morbidity and mortality. No reliably effective treatment has yet been established. We present 10 patients with haematological malignancies who underwent an allogeneic stem cell transplant and developed sclerodermatous GVHD. Donor lymphocyte infusion administered for relapse or reducing donor T-cell chimerism was a known trigger for sclerodermatous GVHD in four of the patients. Treatment with immunosuppressants, psoralen plus ultraviolet A (PUVA) and extracorporeal photopheresis has been largely unsuccessful in their management. Intensive immunosuppression including the use of anti-CD20 monoclonal antibody may have contributed to relapse of leukaemia in one patient 10 years after her transplant. Sclerodermatous GVHD may occur without a preceding lichenoid stage. Clinical heterogeneity is common, although sclerodermatous GVHD has a predilection for the limbs. Treatment options are largely unsatisfactory if conventional immunosuppression fails. PUVA may give some symptomatic benefit and extracorporeal photopheresis seems to be less efficacious than previously published work suggests.

[Surgery in hemopathies: experience in ambulatory care and day surgery]. / La chirurgia nelle emopatie: esperienza in regime ambulatoriale ed in "day surgery".

The one day surgery experience of our team developed in many years of a Special Surgical Service in Haematologic Diseases (within the III Surgical Department directed by Prof. G. Di Matteo of the University of Rome "La Sapienza") is herein reported. From 1989 to December 1995, 2,126 haematologic patients (1127 M, 999 F) were operated in day-surgery regimen. Five-hundred-fifty-six patients were over 65 years old. In most cases surgery was required for diagnostic purposes to ascertain the type, the stadiation or re-stadiation of the haematologic disease. Five-hundred-eighty-three operations were carried on the axillary region, 825 on the cervical region, 202 on the supraclavicular region and 163 on the groin region. In 729 patients a diagnosis of non-Hodgkin lymphoma was obtained, while 308 patients resulted affected by Hodgkin lymphoma. In 124 patients metastases from solid tumors (pulmonary, mammary, thyroidal adenocarcinoma, etc.) were found at histologic examination of the specimen. Furthermore, other types of pathologies such as lateral neck cysts, salivary gland adenomas, schwannomas, groin and crural hernias were identified. Outpatient surgery and one day surgery represent a valid procedure for the early diagnosis of haemotologic diseases also taking into account the low cost and the minimal invasiveness.

Autologous peripheral blood stem cell transplantation after high dose therapy in patients with advanced lymphomas.

Thirty-eight patients with refractory or relapsed non-Hodgkin's lymphoma (19 patients) or Hodgkin's disease (19 patients) were treated with salvage therapy. The peripheral stem cell collection was performed during hematologic recovery after myeloablative chemotherapy. In eight patients with Hodgkin's disease the number of CFU-GM collected was less than 0.5 x 10(4)/kg and these patients were excluded for stem cell transplantation. In the remaining 30 patients, a median of 4 x 10(4) CFU-GM/kg was collected (range 0.8-100 x 10(4)/kg) by three leukaphereses in 25 patients and six to 11 leukaphereses in five patients. Conditioning regimens were CBV (eight), BEAM (six), BEAC (10) and cyclophosphamide + total body irradiation (TBI) (six). Without TBI, the mean time for reaching a granulocyte count greater than 0.5 x 10(9)/l was 18 days and for a platelet count greater than 50 x 10(9)/l was 19 days in 23 out of 24 patients. With TBI, in five patients the mean time for reaching a granulocyte count greater tahn 0.5 x 10(9)/l was 37 days and for a platelet count greater than 50 x 10(9)/l was greater than 100 days. Complications were minor. There was only one toxic death. The outcome in these patients was similar to that observed in patients who received autologous bone marrow transplantation for advanced lymphomas. In conclusion, we observed good hematologic recovery except when TBI was used in the conditioning regimen.

High frequency of antithrombin 3 and protein C deficiency following autologous bone marrow transplantation for lymphoma.

To investigate the possibility that a hypercoagulable state develops during autologous bone marrow transplantation (BMT), we measured levels of circulating natural anticoagulants and fibrinolytic proteins before and weekly during the hospital course of 18 patients undergoing autologous BMT for Hodgkin's and non-Hodgkin's lymphoma. Patients received either weekly (standard dose group) or daily (high dose group) vitamin K supplements with their total parenteral nutrition. By day 14 there had been a significant drop in protein C activity (mean of 95% of normal to 52%), protein C antigen (mean of 105% of normal to 70%), and antithrombin 3 activity (111% of normal to 83%), and an increase in fibrinogen (471-621 mg/dl) and tissue plasminogen activator (6.9-13.8 ng/ml). No changes were seen in free or total protein S, plasminogen activator inhibitor, prothrombin time or partial thromboplastin time. The decreases in protein C and antithrombin 3 persisted through day 28 after transplantation. The drop in protein C correlated strongly with decrease in serum albumin, suggesting impaired synthesis of these proteins by the liver. No differences were seen in any of these parameters between the standard and high dose groups. Deficiencies in anticoagulant proteins antithrombin 3 and protein C and a rise in fibrinogen without a concomitant improvement in fibrinolytic variables create a potentially hypercoagulable state which may contribute to the thrombotic complications of autologous BMT.

CT quantitation of tracheal cross-sectional area as a guide to the surgical and anesthetic management of children with anterior mediastinal masses.

Pediatric patients presenting with anterior mediastinal masses between January 1980 and November 1988 were reviewed to assess the correlation between tracheal cross-sectional area and anesthetic risks. Forty-two patients had evaluable computed tomography (CT) scans and underwent a surgical procedure. Thirty-four patients had Hodgkin's disease, six had non-Hodgkin's lymphoma, and two had mediastinal teratoma. Tracheal cross-sectional areas were greater than 75% of expected in 19 cases, greater than 50% to 75% in 16 cases, greater than 25% to 50% in five cases, and less than or equal to 25% in two cases. The presence or extent of symptoms did not correlate well with the degree of tracheal narrowing shown by CT scan except for orthopnea. Local anesthesia was used primarily in patients with significant tracheal narrowing (tracheal size was less than or equal to 56% in 5 of 6 patients). General anesthesia with spontaneous ventilation by mask was performed in four patients with tracheal areas of 33%, 73%, 76%, and 98% of expected. General endotracheal anesthesia was utilized in the remaining 32 patients, only three of whom had tracheal areas of less than 50% of expected (down to 30%, 26%, and 24% of expected) and one received preoperative radiotherapy (26%). None of these 32 patients had symptoms of orthopnea or dyspnea at rest, and only one had dyspnea on exertion. All tolerated anesthesia without difficulty. No patient in this series suffered respiratory or cardiovascular collapse during surgery. Adequate biopsy material was obtained in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)