Matched-Pair Analysis of Transplant from Haploidentical, Unmanipulated Bone Marrow Donor versus HLA Identical Sibling for Patients with Hematologic Malignancies.

A matched-pair analysis of transplant-related outcomes was carried out in 116 of 255 consecutive patients who received transplants from an HLA identical sibling (n = 58) or haploidentical related donor (n = 58). The 2 patient series were matched with 9 variables: period of transplant, patient and donor age, sex, diagnosis, disease phase, conditioning regimen, donor-recipient sex, and cytomegalovirus (CMV) status combinations. As graft-versus-host disease (GVHD) prophylaxis, all patients received the standard cyclosporine and methotrexate association with the addition of anti-thymocyte globulins, mycophenolate mofetil, and basiliximab in haploidentical, unmanipulated bone marrow recipients. Anti-infectious management, transfusion policy, and supportive care were identical for all patients. By comparing the 2 patient series, no statistically significant difference was observed for the cumulative incidence of advanced acute and extensive chronic GVHD, transplant-related mortality, and relapse. With a median follow-up of 3.5 years, the 5-year disease-free survival was 37% ± 6% and 36% ± 6% for HLA identical sibling and haploidentical recipients, respectively. The results of transplant from HLA identical siblings and haploidentical donors are comparable. Regardless of the HLA matching, other factors known to affect the transplant outcomes, such as donor-recipient age, sex, and CMV status combinations, might drive the search for the best donor.

The Rome Transplant Network model compared to the Italian Bone Marrow Donor Registry activity for unrelated donor search process and transplant efficiency for hematologic malignancy.

BACKGROUND: From 2011 to 2014, a total of 71% of the 3834 patients with hematologic malignancies successfully identified a matched unrelated donor (MUD) through the Italian Bone Marrow Donor Registry (IBMDR), corresponding to a transplant efficiency of 62%. STUDY DESIGN AND METHODS: From 2006, the Rome Transplant Network (RTN) followed a hierarchical selection strategy for the alternative donor search: first MUD, second cord blood, and third haploidentical donor. Using a low-resolution HLA, a preliminary query (PQ) was performed in all cases with assignment of good or poor score if more or less than 10 MUDs were identified in Bone Marrow Donors Worldwide. Herein we assessed the utility of PQ and of high-resolution (HR) HLA from the start of the search. Moreover, we compared the donor identification and the transplant efficiency between IBMDR and RTN. RESULTS: At RTN 79% of 417 patients met a good PQ with a 50% MUD identification versus 12.5% with poor PQ. Our policy led to 78 and 74% of alternative donor identification and transplant efficiency, respectively, higher than IBMDR data equal to 71% (p = 0.007) and 62% (p < 0.0001). The timing for donor identification was significantly reduced using HR HLA at the start of the search from 88 to 66 days at IBMDR (p < 0.001) and from 61 to 41 days at RTN (p < 0.001). CONCLUSIONS: Both PQ and HR HLA at the start of the process represents a useful tool to address the search towards the best and timely donor choice. Moreover, establishing a specific donor policy significantly improves the transplant efficiency.

Fibrin glue therapy for severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) occurring after allogeneic transplantation significantly affects quality of life and, in some cases, becomes intractable, increasing the risk of death. To date, its therapy is not established. We used the hemostatic agent fibrin glue (FG) to treat 35 patients with refractory post-transplantation HC. Of 322 adult patients undergoing an allogeneic transplantation for hematological malignancy, 35 developed grade ≥ 2 HC refractory to conventional therapy and were treated with FG, diffusely sprayed on bleeding mucosa by an endoscopic applicator. The cumulative incidence of pain discontinuation and complete remission, defined as regression of all symptoms and absence of hematuria, was 100% at 7 days and 83% ± 7%, respectively, at 50 days from FG application. The 6-month probability of overall survival for all 35 patients and for the 29 in complete remission was 49% ± 8% and 59% ± 9%, respectively. In the matched-pair analysis, the 5-year probability of overall survival for the 35 patients with HC and treated with FG was not statistically different from that of the comparative cohort of 35 patients who did not develop HC (32% ± 9% versus 37% ± 11%, P = not significant). FG therapy is a feasible, effective, repeatable, and affordable procedure for treating grade ≥2 HC after allogeneic transplantation.

[Membranous glomerulonephritis secondary to allogeneic stem cell transplant: review of the literature]. / La glomerulonefrite membranosa secondaria al trapianto allogenico di cellule staminali: rassegna della letteratura.

Renal injury associated with hematopoietic stem cell transplant (HSCT) may be related to a combination of factors. Chronic graft-versus-host disease (cGVHD) is the most common complication of allogeneic HSCT. Although the kidneys are not considered the primary target organs for GVHD, chronic impairment of renal function may occur in 20% to 60% of HSCT patients. Membranous glomerulonephritis (MG) is the most frequent renal complication observed in patients who develop nephrotic syndrome after allogeneic HSCT. In this setting, the pathogenesis of MG is not clearly understood and the most appropriate treatment approach has not been established. In order to summarize the current knowledge on this issue, a review of the pertinent literature has been performed. The available data on MG diagnosed in patients submitted to allogeneic HSCT were identified using the MEDLINE database (last accessed: Jan 30, 2012). Fifty-nine patients with allogeneic HSCT-related MG with a median age of 43 years were identified. MG occurred at a median time of 17 months after allogeneic HSCT. A history of acute or concomitant clinically apparent cGVHD was present in 69% and 31% of cases, respectively. cGVHD, nonmyeloablative conditioning regimens, immunosuppression withdrawal, and the use of peripheral blood stem cell grafts were identified as risk factors. Among the 53 patients with available outcome data, complete remission, partial response, and inefficacy of treatment were recorded in 65%, 22% and 13% of cases, respectively. MG after allogeneic HSCT seems to be etiologically related to subclinical or overt cGVHD, which flares up after discontinuation of immunosuppression. The available measures can induce sustained long-term remission in about two-thirds of affected patients.

Platelet gel for treatment of mucocutaneous lesions related to graft-versus-host disease after allogeneic hematopoietic stem cell transplant.

BACKGROUND: Platelet (PLT) gel has been successfully used in tissue regeneration of diabetic/surgical wounds through the releasing of growth factors such as basic fibroblast growth factor and PLT-derived growth factor. Therefore, the PLT gel could represent a therapeutic tool in treating the deep and painful wounds sometimes occurring during graft-versus-host disease (GVHD). STUDY DESIGN AND METHODS: The aim of this study was to verify the efficacy and safety of PLT gel for treating GVHD ulcers. Allogeneic hemocomponents were used to obtain PLT gel with an automated system for the on-site preparation and application of patient (autologous) or healthy blood donor (allogeneic)-derived fibrin sealant or PLT-rich fibrin (Vivostat system, Vivostat A/S). Six patients with multiple lesions involving dermis (Grade I, n = 2), subcutaneous (Grade II, n = 4), or oral mucosa and related to GVHD underwent PLT gel as local therapy. RESULTS: After the second PLT gel application, the pain disappeared in all cases and the granulation tissue was observed in the four patients with Grade II lesions. After a median of eight PLT gel applications (range, 4-10), five of six patients showed a complete response, while one patient with a partial response died early from multiorgan failure. No side effects were documented. CONCLUSION: These preliminary data show that the PLT gel may be used as a safe and effective tool in the management of mucosal skin lesions related to the GVHD.

Mucositis in patients with hematologic malignancies: an overview.

Mucosal barrier injury (mucositis) is a common complication of many treatments used in hematologic malignancies, affecting most patients whose neoplasms are treated with intensive chemotherapy, and virtually all those receiving myeloablative conditioning regimens prior to hematopoietic stem cell transplantation. Mucositis has been identified as a critical risk factor for infections and is a major driver of analgesic and total parenteral nutrition use. Patients with this complication require careful analgesic therapy, additional nursing care and longer hospitalization. To date, the measures to prevent and treat this potentially devastating complication are inadequate and limited to the control of pain, infections, bleeding and nutrition. Nevertheless, in the last decade, a better insight into the pathogenesis of the mucosal damage has led to the development of novel therapeutic options which potentially could allow a targeted approach to mucositis.

Home care management of patients affected by hematologic malignancies: a review.

Home care (HC) has an increasingly expanding role in the global management of patients affected by hematologic malignancies. Integrated strategies, including causal-targeted and supportive treatments according to hematologic expertise and a holistic approach inspired by the philosophy and practice of palliative medicine, may allow suitable management and the possibility for most patients to stay at home. Physical, social and psychological needs of patients are likely to vary according to the course of their disease and the treatments they are receiving. Therefore, consideration should be given to different models of care and how to tackle patients' diverse needs, as outlined by reported experiences which claimed that HC can provide appropriate solutions not only for terminally and chronically ill patients but also for those in other phases of disease. According to these studies and to our own experience, when appropriate measures and structured operating models are adopted, HC results in a safe, effective and economically realistic alternative to traditional in-hospital treatment. Therefore, all efforts should be made to overcome budget and administrative barriers and to ensure a more widespread use of this model of care.

A prospective study comparing quantitative Cytomegalovirus (CMV) polymerase chain reaction in plasma and pp65 antigenemia assay in monitoring patients after allogeneic stem cell transplantation.

BACKGROUND: Low levels of Cytomegalovirus (CMV) viral load are frequently detected following allogeneic stem cell transplantation (SCT) and CMV disease may still develop in some allogeneic SCT patients who have negative pp65-antigenemia (pp65-Ag) or undetectable DNA. Pp65Ag is a sensitive method to diagnose CMV infection. Quantitative CMV-DNA PCR assay in plasma has been proposed to monitor CMV infection in SCT patients. We evaluated the clinical utility of pp65Ag and PCR assay in plasma of SCT recipients. METHODS: In a prospective longitudinal study, 38 consecutive patients at risk of CMV infection (donor and/or recipient CMV seropositive) were weekly monitored for CMV infection by both quantitative CMV-PCR in plasma (COBAS AMPLICOR CMV MONITOR) and pp65 Ag, during the first 100 days after SCT. RESULTS: A total of 534 blood samples were simultaneously analysed for pp65Ag and PCR. Overall, 28/38 patients (74%) had active CMV infection within 100 days from SCT. In 16 patients, CMV was first detected by pp65 Ag alone; in 5 patients by both methods and in 6 by PCR assay alone; one patient had CMV biopsy-proven intestinal disease without pp65Ag and PCR assays positivity before CMV disease. Overall, three patients developed intestinal CMV disease (7.9%): one had negative both pp65Ag and PCR assays before CMV disease, one had disease and concomitant positivity of both methods, while in the remaining patient, only pp65Ag was positive before CMV disease. CONCLUSION: Plasma PCR(COBAS AMPLICOR CMV MONITOR) and pp65Ag assays were effective in detecting CMV infection, however, discordance between both methods were frequently observed. Plasma PCR and pp65Ag assays may be complementary for diagnosis and management of CMV infection.