Incidence, risk factors and therapy response of acute graft-versus-host disease after myeloablative hematopoietic stem cell transplantation with posttransplant cyclophosphamide.

Posttransplant cyclophosphamide, sirolimus and mycophenolate mofetil (PTCy/siro/MMF) constitutes an innovative and well-tolerated acute graft-versus-host disease (aGVHD) prophylaxis after allogeneic stem cell transplantation (allo-HSCT), but risk factors for aGVHD incidence and therapy failure in this setting are scarce. This study prospectively registered all consecutive adult patients with hematologic malignancies who received a myeloablative allo-HSCT using PTCy/siro/MMF prophylaxis at our institution between 2017 and 2023. A total of 385 patients were included, of whom 44%, 34% and 22% were transplanted from matched sibiling, matched unrelated and haploidentical donors, respectively. The 180-day cumulative incidence of aGVHD was 21% (95% confidence interval [CI] 17-25%) for grade II-IV and 11% (95% CI 8-14%) grade III-IV aGVHD. The use of haploidentical donors was associated with an increased risk of severe aGVHD. Among 75 patients receiving first-line systemic corticosteroids, 49% achieved a sustained complete response, while 23% and 24% developed steroid-dependent (SD-aGVHD) and steroid-refractory aGVHD (SR-aGVHD), respectively. SR-aGVHD was associated with worse salvage treatment response and overall survival compared to SD-aGVHD. The 1-year cumulative incidence of aGVHD-related mortality was 5.4% (95% CI, 3.3-8.1). Risk factors for aGVHD-related mortality included haploidentical donors, older donors, diagnosis of myeldysplastic neoplasms, and grade IV aGVHD. This study confirms a low incidence aGVHD with PTCy/siro/MMF prophylaxis. SR-aGVHD showed poorer response to salvage therapies and worse survival, while haploidentical donors and older donor age were negative predictors for aGVHD-related deaths.

Immune thrombotic thrombocytopenic purpura in older patients: Results from the Spanish TTP Registry (REPTT).

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.

Use of reverse-transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen, cytokeratin 19, and maspin in the detection of tumor cells in leukapheresis products from patients with breast cancer: comparison with immunocytochemistry.

This study evaluates the role of reverse-transcriptase polymerase chain reaction (RT-PCR) assay for carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and maspin transcripts to identify breast cancer cells (BCC) in leukapheresis products (LP) collected from breast cancer (BC) patients and compares these results with those obtained using immunocytochemistry (IC). Eighty-four LP obtained from 33 patients with stage II-III BC and control subjects without BC were screened for the presence of BCC by IC and CK19, CEA, and maspin expression using RT-PCR. CEA RT-PCR and IC were the only specific markers, as no false positives were detected in any patients without BC. CK19 RT-PCR gave 11% false positives, whereas maspin RT-PCR with 25% was the most unspecific marker. In LP from BC patients, positive results were observed in 70% and 63% for CK19 and CEA RT-PCR, respectively. For maspin RT-PCR, this percentage was 22%, and for IC it was 17%. There was a good correlation between the CEA and CK19 RT-PCR (p = 0.018). No correlation between CEA and CK19 RT-PCR and IC was found, and although 5 of the 6 IC+ samples were CEA+/CK19+, great discrepancies in the group of IC- samples were observed. Our data suggest that RT-PCR assays for CEA and, to a lesser extent, for CK19 have more sensitivity and specificity than IC to detect BCC in LP.

Minimal illegitimate levels of cytokeratin K19 expression in mononucleated blood cells detected by a reverse transcription PCR method (RT-PCR).

Cytokeratin K19 (CK19) expression was evaluated by a reverse transcription PCR method (RT-PCR) in the RNA obtained from peripheral blood stem cell collections (PBSC) from four patients with breast cancers (BC) and 34 mononucleated blood cell (MBC) negative controls (17 PBMC from normal subjects 12 PBSC from different types of leukaemias--M3, M4Eo, M2, etc.--and two from patients with Hodgkin's lymphoma; and three bone marrow (BM) collections). Two BC tissues were taken as positive controls. The method studied (Datta YH, Paul T, Adams PT, Drobyski WR. Sensitive detection of occult breast cancer by reverse transcription polymerase chain reaction. J Oncol 1994;12:475-8) is sensitive enough to allow the detection of CK19 transcripts in a 10(-6) dilution of cDNA reverse transcribed from 1 microgram of BC RNA, but CK19 transcripts were also detected in 64% of the RNA obtained from the MBC controls. However, the amplified product detected in the control samples represents the transcript of the CK19 gene as confirmed by the results of Mae III digestion. It should be pointed out that although the CK19 expression was detected, the levels of expression in PBMC were almost negligible for they disappeared at 1:5 cDNA dilution. Moreover, a direct relationship between the number of BC cells added to PBMC and the increasing dilution levels of the cDNA necessary to prevent CK19 expression was observed. This allows us to conclude that the cDNA dilutions make it possible to distinguish the false from the true positive samples and that, in addition, the cDNA dilutions inform about the degree of BC cell contamination.

[Thrombotic thrombopenic purpura and HIV infection. Apropos of a case]. / Púrpura trombótica trombopénica e infección VIH. A propósito de un caso.

In the past years, more than thirty cases of thrombotic thrombocytopenic purpura (TTP) had been described associated to infection by the human immunodeficiency virus. Some authors have suggested the presence of a causal relationship between both entities, although the common nexus is still unknown. It usually has a fulminant onset, affecting all the risk groups and in any stage of the disease. The clinical manifestations are similar to the classical forms, as well as the evolution and response to treatment. We present a new clinical case, typical in its presentation and its good response to treatment with plasmatic spares associated to PFC and steroid infusion. We believe that the presence of clinical signs suggesting TTP in a patient would necessarily discard the presence of HIV infection and, the other way round, the presence of clinical signs suggesting TTP in a patient with HIV infection would determine the onset of an early and aggressive treatment based on plasmatic spares, given that the prognosis is linked to an early onset of the treatment.