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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., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Ninety-seven patients affected by high-risk hematological malignancies underwent G-CSF primed, unmanipulated bone marrow (BM) transplantation from a related, haploidentical donor. All patients were prepared with an identical conditioning regimen including Thiotepa, Busilvex, Fludarabine (TBF) and antithymocyte globulin given at myeloablative (MAC = 68) or reduced (reduced intensity conditioning (RIC) = 29) dose intensity and received the same GvHD prophylaxis consisting of the combination of methotrexate, cyclosporine, mycofenolate-mofetil and basiliximab. Patients were transplanted in 1st or 2nd CR (early phase: n = 60) or in > 2nd CR or active disease (advanced phase: n = 37). With a median time of 21 days (range 12-38 days), the cumulative incidence (CI) of neutrophil engraftment was 94 ± 3%. The 100-day CI of III-IV grade acute GvHD and the 2-year CI of extensive chronic GvHD were 9 ± 3% and 12 ± 4%, respectively. Overall, at a median follow-up of 2.2 years (range 0.3-5.6), 44 out of 97 (45%) patients are alive in CR. The 5-year probability of overall survival (OS) and disease-free survival (DFS) for patients in early and advanced phase was 53 ± 7 vs 24 ± 8% (P = 0.006) and 48 ± 7 vs 22 ± 8% (P = 0.01), respectively. By comparing MAC with RIC patient groups, the transplant-related mortality was equivalent (36 ± 6 vs 28 ± 9%) while the relapse risk was lower for the MAC patients (22 ± 6 vs 45 ± 11%), who showed higher OS (48 ± 7 vs 29 ± 10%) and DFS (43 ± 7 vs 26 ± 10%). However, all these differences did not reach a statistical significance. In multivariate analysis, diagnosis and recipient age were significant factors for OS and DFS. In conclusion, this analysis confirms, on a longer follow-up and higher number of patients, our previous encouraging results obtained by using MAC and RIC TBF regimen as conditioning for G-CSF primed, unmanipulated BM transplantation from related, haploidentical donor in patients with high-risk hematological malignancies, lacking an HLA-identical sibling or unrelated donor and in need to be urgently transplanted.

Background: The prevention of oral mucositis (OM) in the management of hematological malignancies continues to represent an unmet clinical need. Addressing this issue has major clinical implications as OM can also greatly impair patient's quality of life., Objectives: To review currently available measures and investigational agents to prevent OM in hematological patients., Methods: we searched for OM and related issues using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed., Results/conclusions: Many agents targeting different mechanisms of mucosal damage have been applied in order to prevent OM; most of them have failed or its efficacy has not been fully demonstrated. Palifermin is the first pharmaceutical/biological agent approved for the prevention of OM; its use is currently restricted to patients who have received radiotherapy-containing conditioning regimens prior to autologous hematopoietic stem cell transplantation. No clear benefit by this agent has been demonstrated outside of this specific setting and its application should be limited to clinical trials. Other interventions, such as other growth factors and non mitogenic measures are under investigation or in development and their application in the hematological setting is expected in the short term.

The management of hematological malignancies (HM) in renally impaired patients may be a difficult task. Indeed, the kidney represents a major elimination pathway for many chemotherapeutic agents and their metabolites, whose serum levels are not usually measured in daily clinical practice. In addition, many antineoplastic drugs have a narrow therapeutic index for which they require dose adjustment when administered to patients with renal failure. Only limited data regarding the use of chemotherapy in patients with renal impairment and in those on dialysis are available. Indeed, renal patients with HM are often excluded from most clinical trials. Thus far, in order to provide recommendations, we have reviewed the pertinent literature, gathering information from published guidelines regarding chemotherapy in patients with kidney dysfunction and from articles describing the use of individual agents in renal patients with HM.

Pain is frequently experienced by patients with hematological malignancies, although it often receives little attention. Different underlying causes and mechanisms may sustain several pain syndromes in hematological malignant patients. Pain may be due to disease itself, to disease-related complications, to iatrogenic causes or may be associated with unrelated medical conditions. The management of pain in this setting requires a multidisciplinary approach, integrating analgesics and causal interventions. An accurate diagnostic assessment and the identification of the underlying causes and pathogenetic mechanisms may dictate the treatment approach. For most pain patients, the WHO's three-step analgesic scale for cancer pain relief can provide adequate relief with oral options, although difficult-to-treat pain syndromes, requiring a more complex treatment approach, may also be observed.

Mucositis is the result of the cytotoxic effects of many treatments given for hematological malignancies (HMs); it represents a major source of potentially devastating clinical complications and portrays negative consequences on the patient's management, such as a longer hospitalization, the need of analgesic and total parenteral nutrition use, and increased costs. The available measures for the prevention and treatment of mucositis have been substantially palliative, being limited to the control of pain, infection, bleeding and nutrition. However, in the last decade, a better insight into the complex pathogenesis of MBI has led to the development of novel therapeutic options, such as palifermin, which can provide tools potentially allowing a targeted approach to mucositis.

Background: In the management of hematological malignancies, chemotherapy-induced mucositis is an increasingly recognized problem, leading to potentially severe clinical complications, treatment delays, increased costs and impairment of patient's quality of life. Many forms of cytotoxic treatments given in this setting may induce several degrees of mucositis. In particular, conditioning therapy with hematopoietic stem cell transplantation (HSCT) induces a disruption of the mucosal barrier function throughout the entire gastrointestinal tract facilitating the spreading of bacteria and endotoxin with subsequent increased risk of septicemia and, in the allogeneic setting, a worsening of Graft Versus Host Disease (GVHD)., Objectives: To review the role of palifermin and of other existing and potential treatments for chemotherapy-induced mucositis in the context of current knowledge of pathobiology in the setting of hematological malignancies., Methods: We searched for palifermin and mucositis of any region of the gastrointestinal tract using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed., Results/conclusions: The pathobiology of mucositis is complex, and agents that target mechanisms to prevent mucositis or accelerate healing are highly required. In this regard, palifermin (recombinant human keratinocyte growth factor) has been demonstrated to reduce the severity and the duration of oral mucositis and to significantly improve several treatment outcomes in patients submitted to autologous HSCT; data are insufficient to recommend its use in the non-autologous HSCT settings, although interesting properties of this agent deserves other investigations in order to explore other possible indications.

Patients with advanced hematological malignancies may experience many troublesome hemorrhagic complications requiring hospitalisation during a palliative home care (HC) program. We report on the feasibility of the management of bleeding at home in patients with haematological malignancies admitted in a domiciliary HC program. The occurrence of a major hemorrhage episode (>1 WHO grade) was registered among 469 patients with hematological malignancies in the terminal phase of their disease followed at home. Number, sites, domiciliary treatment (local hemostatic measures, platelet units, hemostatic drugs, packed red blood cells) and outcome of hemorrhagic complications were evaluated. Out of 469 patients, 123 (26%) experienced a bleeding complication; the overall number of hemorrhagic episodes was 232 (49%) with a median number of 2 episodes per patient. Patients with a platelet count lower than 20 x 10(9)/L (P < 0.00005) or with a diagnosis of acute leukemia or in blast crisis of myeloprolypherative disorders (P < 0.00005) showed a significant higher incidence of hemorrhages than other patients. Resolution of bleeding at home was obtained in 206 (88%) of the 232 episodes; platelet units were transfused at home in 188 (81%) cases. Bleeding was the cause of hospitalisation in four cases. Death occurred in 447 of 469 patients: in 26 of them (6%), it was caused by bleeding complications (11 brain hemorrhage, 2 hematemesis, 3 hemoptysis and 10 melena). In this group of patients, bleeding was a relevant clinical problem However, by implementing a domiciliary palliative care program, home management of hemorrhages proved to be a safe and effective choice.

Severe pain syndromes may be recorded during all phases of haematopoietic stem cell transplantation (HSCT) for haematological malignancies: from stem cell mobilization to the long-term post transplant period. Although the major cause of pain in the setting of HSCT is injury to mucosal tissues induced by the conditioning regimen, pain from several other causes has been reported. In this paper, we review pain and its management in the setting of HSCT.

Varicella zoster virus (VZV) outbreak is a significant cause of morbidity in patients suffering from blood-related malignancies, occurring mostly among those affected by lymphoproliferative disorders and in those receiving haematopoietic stem-cell transplantation. The elucidated pathological mechanisms of VZV-related painful complications have provided the rationale for acute zoster pain (AZP) and post-herpetic neuralgia (PHN) treatment with antiviral therapy combined with neuroactive agents, such as tricyclic or anticonvulsant agents. The role of opioids in this setting is less clearly established. We successfully treated (with oxycodone) 12 consecutive patients suffering from AZP and long-lasting PHN resistant to several agents, including anticonvulsants and analgesics. Our experience is reported together with a brief overview of the management of these often distressing and intractable complications.

We report on epidemiology, features, outcome, and domiciliary management of pain in patients with advanced hematological malignancies followed by an experienced hospital-based home care (HC) team. Out of 469 patients, 244 (52%) experienced a total of 284 pain syndromes. Pain intensity was rated from mild to moderate in 31% and from moderate to severe in 69% of them. The diagnosed pain mechanisms were deep somatic in 56%, superficial somatic in 15%, visceral 14%, mixed 8%, and neuropathic in 7% of pain syndromes, respectively. Incident pain was observed in 38% of all pain syndromes. In every diagnostic group, deep somatic pain was prevalent. Moreover, 85% of visceral pain syndromes were observed in patients affected by non-Hodgkin's lymphoma (NHL). In addition, out of 284 pain syndromes, 150 (51%) were caused by bone involvement. The most frequent recognized pain provocative mechanisms were bone marrow expansions, osteolysis, lymph node enlargement, and mucositis. In our experience, an approach based on the association of causal therapies and analgesics allows optimal control of most pain syndromes. Therefore, pain is a major problem in patients affected by advanced hematological malignancies, and its management can be effective and feasible when carried out by a skilled HC team.

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.

High-dose chemotherapy and radiation used as a preparative regimen for allogeneic stem cell transplantation (SCT) produces a considerable morbidity and mortality. An alternative strategy, developed to reduce transplant-related toxicity and to induce graft versus malignancy effect in the presence of full hematopoietic engraftment, includes the application of RIC that provide sufficient immunosuppression. We studied the efficacy and toxicity of RIC followed by allogeneic SCT in elderly patients or with relative contraindications to conventional SCT. In all, 22 patients with hematologic malignancies and HLA-identical sibling donors were included in this study. All patients were either refractory to therapy or beyond first complete remission (CR). The majority of patients received fludarabine 120 mg/m(2)+thiotepa 10 mg/kg as conditioning regimen and cyclosporine as graft versus host disease (GVHD) prophylaxis. Organ toxicity was acceptable and all evaluable patients achieved engraftment. Three patients (15%) showed grade >II aGVHD; extensive chronic GVHD occurred in three out of 15 evaluable patients (20%). With median follow-up of 63.5 months, survival was 31%, disease-free survival (DFS) was 23%. All the durable responses occurred in patients who developed GVHD. Transplant related mortality (TRM) at 100 days was 27.3%, 67% of that caused by infections, while 6-year cumulative incidence of TRM was 38%. Our data show that RIC: (1). allows the engraftment of HLA-matched hematopoietic stem cells (2). provide durable responses in patients not eligible for conventional SCT exploiting the graft-versus-malignancy effect and (3). is loaded by an high rate of fatal infections.