Allogeneic stem cell transplantation for myelodysplastic syndrome

Although it is only used to treat a minority of patients with myelodysplastic syndromes, stem cell transplantation (SCT) is the only proven curative treatment for this condition. Because MDS occurs in a population of older adults with significant comorbidities, reduced-intensity conditioning (RIC) regimens have been particularly important in extending safe SCT to the large MDS population over the age of 60 years. Extension of the unrelated donor pool together with the introduction of umbilical cord blood transplants in adults has extended the number of patients with suitable donors. Nevertheless overall mortality from SCT is greater than 50% because of relapse and non-relapse mortality (NRM). New developments to improve outcome include the tailoring of the transplant approach to the individual based on age and comorbidity, and the use of pretransplant chemotherapy to reduce disease bulk prior to transplant, as well as the introduction of post-transplant immunotherapy (pre-emptive donor lymphocyte infusions) and chemotherapy to prevent relapse. Further improvements in transplant outcome await better ways to reconstitute immunity and amplify the graft-versus-leukemia (GVL) effect without causing graft-versus-host disease (GVHD), as well as further extension of the donor pool and exploration of risk-adapted regimens for the population of MDS in their seventh to eighth decade.     

Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome

Allogeneic hematopoietic stem cell transplantation (SCT) is well accepted as a curative treatment approach for younger patients with myelodysplastic syndrome (MDS) and has become one of the most frequent indications for allogeneic SCT as reported to the Center for International Blood and Marrow Transplant Research. However, MDS patients are usually elderly with a median age of approximately 75 years at diagnosis. Large register studies have confirmed the feasibility of the procedure in elderly MDS patients; and in the register of the European Group for Blood and Marrow Transplantation, one-third of the allogeneic transplant procedures for MDS were performed in 2010 in patients older than 60 years. Despite its curative potential, its role in the treatment of elderly MDS patients is less defined. Because of the inherent complications of the transplantation leading to treatment-related mortality and the risk of relapse, a careful calculation of the benefit for each patient is mandatory, taking into account comorbidities, disease status, donor selection, and effective nontransplant therapies. Prospective multicenter studies are needed to define optimal intensity of the conditioning regimen, timing of transplantation within a treatment algorithm, including drug-based therapies, and posttransplant strategies to reduce the risk of relapse.     

Allogeneic hemopoietic stem cell transplantation in patients with myelodysplastic syndrome or myelofibrosis

Myelodysplastic syndrome (MDS) and myeloproliferative disorders associated with myelofibrosis (MF) are stem cell disorders, and hemopoietic stem cell transplantation (HSCT) is currently the only therapy with curative potential. Among patients with less advanced MDS, 3 year survivals of 65% to 70% are achievable with HLA-identical related and HLA-matched unrelated donors. The probability of relapse is < 5%. Among patients with advanced disease (> or = 5% marrow blasts), about 35 to approximately 45% and 25 to approximately 30%, respectively, are surviving in remission after transplantation from related or unrelated donors. The incidence of post-transplant relapse is 1035%. Criteria of the International Prognostic Scoring System (IPSS), originally developed for nontransplanted patients, also predict survival following transplantation. Patients with MF, either idiopathic or on the basis of pre-existing disorders, are also transplanted successfully with stem cells from related or unrelated donors. Transplants early in the disease, before leukemic transformation, are successful in 60 to approximately 80% of patients. Success rates are lower in patients who have developed MDS or leukemia. New conditioning regimens have permitted successful HSCT even in patients in the seventh decade of life. Results with a regimen using a combination of busulfan (targeted to predetermined plasma levels) and cyclophosphamide are particularly encouraging. Improved survival with transplants from unrelated volunteer donors may, in part, reflect selection of donors on the basis of high resolution (allele-level) HLA typing. Nevertheless, transplant-related morbidity and mortality, including graft- vs. -host disease, remain challenges that need to be addressed with innovative approaches.     

Allogeneic hemopoietic stem cell transplantation in patients with myelodysplastic syndrome or myelofibrosis

Myelodysplastic syndrome (MDS) and myeloproliferative disorders associated with myelofibrosis (MF) are stem cell disorders, and hemopoietic stem cell transplantation (HSCT) is currently the only therapy with curative potential. Among patients with less advanced MDS, 3 year survivals of 65% to 70% are achievable with HLA-identical related and HLA-matched unrelated donors. The probability of relapse is <5%. Among patients with advanced disease (?5% marrow blasts), about 35～45% and 25～30%, respectively, are surviving in remission after transplantation from related or unrelated donors. The incidence of post-transplant relapse is 1035%. Criteria of the International Prognostic Scoring System (IPSS), originally developed for nontransplanted patients, also predict survival following transplantation. Patients with MF, either idiopathic or on the basis of pre-existing disorders, are also transplanted successfully with stem cells from related or unrelated donors. Transplants early in the disease, before leukemic transformation, are successful in 60～80% of patients. Success rates are lower in patients who have developed MDS or leukemia. New conditioning regimens have permitted successful HSCT even in patients in the seventh decade of life. Results with a regimen using a combination of busulfan (targeted to predetermined plasma levels) and cyclophosphamide are particularly encouraging. Improved survival with transplants from unrelated volunteer donors may, in part, reflect selection of donors on the basis of high resolution (allele-level) HLA typing. Nevertheless, transplant-related morbidity and mortality, including graft- vs.-host disease, remain challenges that need to be addressed with innovative approaches.     

Allogeneic hematopoietic stem cell transplantation in a patient with HIV-negative recurrent plasmablastic lymphoma: A case report

Introduction:No standard guideline has been established for the treatment of plasmablastic lymphoma (PBL) and prognosis remains extremely poor, given that patients relapse early after chemotherapy and show resistance to commonly used cytostatic drugs.Patient concerns:We present the case of a 52-year-old HIV-negative man who presented with a mass at the left sternoclavicular joint. He had no significant comorbidities and no latent immunosuppression.Diagnosis:The largest lymph node measured was 36 × 19 mm. An excisional biopsy showed diffuse proliferation of large lymphoid cells which were positive for CD38 and CD138, but negative for CD20. He was diagnosed with stage IV PBL with a low IPI.Interventions:The patient was treated with four cycles of induction therapy with bortezomib, epirubicin and dexamethasone. He achieved complete remission. But 3 months after receiving consolidated autologous hematopoietic stem cell transplantation, he relapsed. Allogeneic hematopoietic stem cell transplantation was performed on the patient.Outcomes:The patient achieved remission again and there were no serious complications after allogeneic hematopoietic stem cell transplantation. This patient was followed up once every three months, and to date, he has been disease-free for more than 4 years.Conclusion:The survival of recurrent PBL after autologous hematopoietic stem cell transplantation is very poor. Salvage allogeneic hematopoietic stem cell transplantation may bring long-term survival opportunities for those patients. Further clinical studies are needed to explore the role of allogeneic hematopoietic stem cell transplantation in refractory and recurrent PBL.     

Paraneoplastic polyarteritis nodosa with cerebral masses: case report and literature review

Polyarteritis nodosa (PAN) as a paraneoplastic vasculitis is rarely described, especially in association with squamous cell carcinoma (SCC). Furthermore, only 5% of all PAN patients have central nervous system (CNS) involvement, almost exclusively in the form of cerebral infarction or intracerebral haemorrhage. We report the first case of PAN with multiple immunosuppressant‐responsive, cerebral vasculitic lesions in association with metastatic SCC.     

异基因造血干细胞移植治疗MDS临床研究

目的探讨HLA配型相合异基因造血干细胞移植（allo—HSCT）治疗骨髓增生异常综合征（MDS）的可行治疗方案和疗效。方法以HLA配型相合的骨髓移植治疗MDS患者6例,预处理方案为非清髓性预处理方案1例,清髓性预处理方案5例;以霉酚酸酯、环孢菌素A加短疗程的甲氨喋呤预防移植物抗宿主病（GVHD）。结果6例患者均造血重建。5例清髓性预处理方案仍然无病存活,非清髓性预处理方案1例移植后出现MDS,于移植后17个月死亡。移植后最长无病存活时间已达8a。移植期间发生Ⅰ、Ⅱ°急性移植物抗宿主病（aGVHD）4例。结论allo-HSCT治疗MDS可行、有效,清髓性预处理方案可能对于长期稳定植入有利。     

Successful reduced-intensity stem cell transplantation in a patient with myelodysplastic syndrome combined with Sweet's syndrome

A 53-year-old male with myelodysplastic syndrome developed Sweet's syndrome extensively over his left iliac and inguinal regions that was refractory to standard treatment with corticosteroids and chemotherapy, received a stem cell transplant from an HLA-matched unrelated donor, conditioned by reduced-intensity regimen. The patient achieved complete hematological remission, and the cutaneous lesions improved gradually and then disappeared completely despite the patient receiving granulocyte colony-stimulating factor after transplantation and developing acute graft-versus-host disease.     

Donor cell myelodysplastic syndrome after allogeneic stem cell transplantation responding to donor lymphocyte infusion: case report and literature review

Allogeneic hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for patients with myelodysplastic syndrome (MDS). Relapses after transplantation however, are not uncommon and are usually due to re-emergence of a recipient derived, neoplastic, stem cell clone. We report a unique case of MDS recurring 5 months after non-myeloablative, sibling, allogeneic SCT. Interestingly, chimerism analysis at relapse showed hematopoiesis to be entirely of donor origin confirming donor cell MDS. Donor lymphocyte infusion (DLI) produced a hematological response lasting several months. Our review of the literature shows donor-derived MDS to be very rare, with only four such cases described previously. In this report, we describe the details of our case and discuss putative mechanisms underlying the genesis of donor cell MDS and the observed response to DLI.     

Conservative management of neurocysticercosis in a patient with hematopoietic stem cell transplantation: a case report and review

Neurocysticercosis, an infection of the central nervous system with the larval stage of the cestode Taenia solium, is common in developing countries but its occurrence and management in allogeneic hematopoietic stem cell transplantation (HSCT) has not been reported previously, to our knowledge. We report the case of an immigrant female patient who underwent a matched‐related allogeneic HSCT for acute lymphoblastic leukemia and was incidentally found to have a solitary viable neurocysticercosis lesion. However, despite severe immunosuppression, the size of the cyst did not increase. More importantly, restoration of the immune system did not induce significant inflammation or seizures. Subsequent follow‐up demonstrated complete resolution of the neurocysticercosis lesion. Thus, in the setting of HSCT, an asymptomatic patient with a single neurocysticercosis lesion was successfully managed without the use of anthelmintics, steroids, or anti‐epileptics.     

Postirradiation morphea and subcutaneous polyarteritis nodosa: case report and literature review

OBJECTIVE: To describe a case of postirradiation morphea and subcutaneous polyarteritis nodosa occurring simultaneously in a patient and to review the literature on postirradiation autoimmune phenomenon and the potential pathogenesis of such changes. METHODS: A 75-year-old woman with breast cancer treated with chemotherapy and radiation who developed postirradiation morphea and subcutaneous polyarteritis nodosa, both inside and outside of the field of radiation, is described. Literature searches were performed on postirradiation morphea and other radiation-related inflammatory cutaneous conditions and the potential pathogenic mechanisms involved. RESULTS: Twenty-five cases of postirradiation morphea and 8 cases of postirradiation panniculitis were reported in the literature. Only 3 cases of morphea with distant vasculitis occurring in the same patient have been reported and each of these patients had features suggestive of an underlying connective tissue disease. This is the first case of morphea and subcutaneous polyarteritis nodosa occurring in the same location both inside and outside the field of radiation. CONCLUSIONS: Postirradiation morphea is an uncommon condition but is being increasingly recognized. Related phenomena following radiation include postirradiation panniculitis and now postirradiation subcutaneous polyarteritis nodosa. Radiation may be responsible for inducing some of the pathogenic changes seen in scleroderma and other autoimmune diseases. Rheumatologists should be aware of these potential complications of radiation treatment.     

Allogeneic stem cell transplantation for myelodysplastic syndromes with bone marrow fibrosis

Background

Bone marrow fibrosis in patients with myelodysplastic syndrome is associated with a poor outcome, but whether the outcome after allogeneic stem cell transplantation is related to the degree of bone marrow fibrosis is unknown.

Design and Methods

Patients with myelodysplastic syndrome and known bone marrow histology (n=721) who underwent hematopoietic stem cell transplantation were classified according to the degree of bone marrow fibrosis into those without fibrosis (n=483), those with mild or moderate fibrosis (n=199) and those with severe fibrosis (n=39) and analyzed regarding engraftment, treatment-related mortality, relapse and survival.

Results

The degree of fibrosis was not associated with disease status or abnormal cytogenetics. The cumulative incidence of engraftment achieved at day +30 in non-fibrotic patients was 93% and was significantly lower in those with mild or moderate fibrosis (89%) and severe fibrosis (75%) (P=0.009). Neutrophil engraftment occurred later in patients with mild or moderate fibrosis and severe fibrosis than in patients without fibrosis (median 17 versus 20 versus 16 days, respectively; P=0.002). The cumulative incidence of relapse at 3 years was significantly higher in patients with severe fibrosis than in those with a lesser degree of fibrosis or no fibrosis (47% versus 28% versus 27%, respectively; P=0.04), resulting in comparable 3-year disease-free survival rates in patients without fibrosis and in those with mild or moderate fibrosis (42% versus 38%, respectively) but a lower disease-free survival rate in those with severe fibrosis (18%; P=0.002). Severe fibrosis remained an independent factor for reduced survival (hazard ratio, 1.9; P=0.006).

Conclusions

Among patients with myelodysplastic syndromes, only severe fibrosis affects survival after hematopoietic stem cell transplantation while patients with mild or moderate fibrosis have an outcome comparable to that of patients without bone marrow fibrosis.     

Pneumatosis intestinalis in a patient with polyarteritis nodosa

Necrotizing enterocolitis of the small bowel in polyarteritis nodosa is rare. In the proper clinical setting, pneumatosis intestinalis and mesenteric air are characteristic of this entity.