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Acute lymphoblastic leukemia (ALL) is a malignant condition of lymphoid progenitor cells that primarily affects the pediatric population, but also adults. The 5-year survival rate is 90% in children and approximately 40% in adults, with survival increasing through the use of peripheral stem cell allotransplantation (SCT). The relapse rate after stem cell transplantation (SCT) in adult acute lymphoblastic leukemia (ALL) patients ranges from 35% to 45%, making relapse a major cause of death in this population. Background: We present an atypical case of late testicular involvement in ALL in a 50-year-old man diagnosed with ALL pro-T in remission post-chemotherapy (GMALL 2003 protocol) and allogeneic stem cell transplantation (alloSCT) from a related donor. Methods: This case describes a 50-year-old male with ALL pro-T who experienced three rare extramedullary relapses post-chemotherapy and alloSCT. Five years after remission, he had a unilateral testicular relapse confirmed by immunophenotyping of spermatic fluid. Results: Despite no bone marrow involvement, he was treated with chemotherapy, intrathecal therapy, and bilateral testicular radiotherapy. He later relapsed in the orbit, controlled by radiotherapy, followed by a third relapse in the heart and colon. Conclusions: This case highlights the unusual sites and consecutive nature of extramedullary relapses in adult ALL.

Adult T-cell Leukemia/Lymphoma (ATLL) is a rare but aggressive malignancy associated with the human T-cell lymphotropic virus type 1 (HTLV-1). ATLL is a challenging malignancy characterized by its aggressive nature and poor prognosis. Despite advancements in treatment, relapse rates remain high. Donor lymphocyte infusion (DLI) is a promising therapeutic option post-hematopoietic stem cell transplantation (HSCT) to prevent relapse. However, the prophylactic use of DLI in ATLL patients remains underexplored. We report the case of a 45-year-old female diagnosed with ATLL. Following induction chemotherapy and successful HSCT, a modified prophylactic DLI regimen was administered, consisting of gradually increasing doses of donor lymphocytes. The patient demonstrated a favorable response with no significant graft-versus-host disease (GVHD) and maintained remission over a 40-month follow-up period, suggesting a potential benefit of this approach. This case highlights the potential efficacy and safety of modified prophylactic DLI in ATLL patients, warranting further investigation. Our findings suggest that modified prophylactic DLI is a viable option for ATLL patients post-HSCT, offering a balance between efficacy and safety. Future research should focus on optimizing DLI protocols and exploring biomarkers for response prediction.

Background/Objectives : Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) resulting from histocompatibility differences between donor and host cells leading to inflammation, tissue damage, and compromised patient outcome. Extracorporeal photopheresis (ECP) is considered as a second-line treatment administered to patients with GVHD who do not respond to corticosteroid treatment or who experience a relapse after an initial response and are therefore classified as steroid refractory (SR). The aim of this study is to evaluate the clinical response rates in both pediatric and adult patients with acute (a) or chronic (c) GVHD and to assess the effectiveness of ECP using the real-world data from a single center. Methods : We performed a retrospective study on 30 patients, including 11 pediatric and 19 adult patients who were treated with ECP as a second-, third-, or fourth-line therapy for (a) and (c) GVHD, alongside corticosteroids and other immunomodulatory medications. The median time from aGVHD onset to ECP was 11.5 days (range: 3 days-9 months), while for cGVHD, the median time was 90 days (range: 2 days-9 months). Results : The overall response rate (ORR) in the aGVHD patient population was 60% with a median of 9 procedures (range: 2-20). For cGVHD patients, the ORR was 70% after a median of 23.5 ECP procedures (range: 8-43). Most patients had skin involvement, with ECP achieving an ORR of 81.8% in aGVHD and 77.7% in cGVHD cases. Conclusions : ECP is a beneficial therapy for patients with (a) and (c) GVHD who have not responded to corticosteroids and other forms of immunosuppressive therapy. Specifically, ECP demonstrated efficacy in improving skin and oral symptoms and permitted reductions in or the elimination of their corticosteroid usage. The study found that extending the duration of ECP treatment was associated with better outcomes, and no detectable complications were observed over a 38-week period.

In order to expand the donor pool and accessibility of the transplant procedure, it was necessary to introduce haplo-identical stem cell transplants in the Fundeni Clinical Institute from 2015. Even if the Romanian population is an ethnically compact white population, many of the patients referred for bone marrow transplant lack a suitable donor. Hematopoietic stem cell transplant from a haplo-identical donor is an alternative option for those patients without an HLA (Human Leucocyte Antigen)-matched donor (sibling or matched unrelated). This procedure was used also as a salvage option for those who experienced engraftment failure or the rejection of the first stem cell graft. In this case series, we present three such cases, with a haplo-transplant used as a salvage protocol (after an engraftment failure or rejection of the first transplanted cells). The patients we present were diagnosed with AML (acute myeloid leukemia) with MDS (myelodysplastic syndrome), MDS-RAEB 2 (myelodysplastic syndrome-refractory anemia with excess blasts 2), and SAA (severe aplastic anemia). In two of the three cases, the engraftment failure may have been due to the conditioning Fludarabine/Busulfan/Cyclophosphamide (Flu/Bu/CFA) used, combined with marrow grafts. In all three cases, the second transplant was of haplo-identical peripheral blood stem cells using Melphalan/Fludarabine (Mel/Flu) conditioning, the cells engrafted properly and the patients experienced complete chimerism, and two of them are alive with an excellent quality of life.

(1) Background: Acute kidney injury (AKI) is a serious complication of hematopoietic stem cell transplantation (HSCT). (2) Methods: The aim was to identify the incidence, severity, and risk factors for AKI during the first 100 days after allo-HSCT; we performed a prospective observational study on 135 consecutive patients. (3) Results: The mean age was 38.3 ± 11.9 years (50.6% females), AKI developed in 93 patients (68.9%), the median time of appearance was 28 days, and the mean serum creatinine at the time of AKI was 1.8 ± 0.8 mg/dL. A total of 36 (38.7%) patients developed stage 1 AKI, 33 (35.5%) patients developed stage 2, and 24 (25.8%) patients developed stage 3; eight (8.6%) patients required temporary hemodialysis, and the mortality rate in these patients was 87.5%. Death was twice as frequent in the AKI subgroup, without statistical significance. Cyclosporine overdose (HR = 2.36, 95% CI: 1.45-3.85, p = 0.001), tacrolimus overdose (HR = 4.72, 95% CI: 2.22-10.01, p < 0.001), acute graft-versus-host disease (aGVHD) (HR = 1.96, 95% CI: 1.13-3.40, p = 0.01), and CRP level (HR = 1.009, 95% CI: 1.007-1.10, p < 0.001) were independent risk factors for AKI. Sepsis (HR = 5.37, 95% CI: 1.75-16.48, p = 0.003) and sinusoidal obstruction syndrome (HR = 5.10, 95% CI: 2.02-12.85, p = 0.001) were found as independent risk factors for AKI stage 3. (4) Conclusions: AKI occurs with high incidence and increased severity after allo-HSCT. Careful monitoring of calcineurin inhibitors and proper management of sepsis may reduce this risk.

Chronic lymphocytic leukemia (CLL) treatment strategies have evolved to include mechanism-driven drugs but now raise new questions regarding their optimum timing and sequencing. In high-risk patients, switching from pathway inhibitors to allogeneic stem cell transplantation (allo-HCT) is still a matter of intense debate. We report the case of a CLL patient with 17 p deletion treated with ibrutinib as a bridge to allo-HCT. Early relapse after allo-HCT urged the initiation of salvage therapy, including donor lymphocytes infusions, ibrutinib, and venetoclax. We aim to outline and discuss the potential benefits of novel therapies, the current role of allo-HCT in CLL, drug timing and sequencing, and the unmet need to improve the long-term outcome of high-risk CLL patients.

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive mature T-cell malignancy caused by the human T lymphoma virus I (HTLV-I) affecting 3-5% of HTLV-1 carriers and is usually diagnosed in endemic regions. Romania is a region with high prevalence of HTLV-1 infection and ATLL and with low median age at diagnosis for aggressive types. We performed a retrospective analysis of post-transplant outcome in the first Romanian patients with ATLL receiving hematopoietic stem cell allotransplant. The study population included eight patients (three males, five females), with median age of 39.5 (range 26-57), with acute (one case) and lymphoma type (seven cases) that received peripheral stem cells (PBSC) from matched related (MRD) and unrelated donors (MUD) after reduced intensity conditioning. Graft versus host disease (GVHD) developed in six patients. Relapse occurred in four cases (50%) at a median time of 5-months post-transplant. Six patients died: four cases with disease-related deaths and two patients with GVHD-related deaths. The median survival post-transplant was 19.5 months (range 2.3-44.2 months). The post-transplant survival at 1-year was 62.5%, at 2-years 50%, and at 3-years 37.5%. In our opinion allogeneic transplant improves outcome in aggressive type ATLL.

Acute kidney injury (AKI) is a common complication after allogeneic stem cell transplantation; however, its incidence and outcome in patients transplanted for multiple myeloma (MM) is unknown. We evaluated the incidence, severity, and risk factors for AKI within the first 30 days after autologous stem cell transplantation (ASCT) for MM. We prospectively followed 185 consecutive patients with MM, without chronic renal replacement therapy, who underwent ASCT; 12.5% of patients had MM-associated amyloidosis. AKI occurred in 19 (10.3%) patients, 8 ± 3 days after ASCT, with 18 patients (9.7%) stage 1 and one patient (0.6%) stage 2 AKI. The development of AKI was not associated with reduced overall survival and recovery of kidney function was evident in 68.4% of patients at 3 months. In Cox regression analysis, preexisting-chronic kidney disease (HR 7.01, CI 95% 2.04-24.09; P = 0.002), serum beta2 microglobulin (HR 3.05, CI 95% 1.10-8.44; P = 0.03), and mucositis grade 3/4 (HR 1.29, CI 95% 1.08-1.53; P = 0.003) were independent risk factors for AKI. Our results suggest that AKI occurs with low incidence and reduced severity after ASCT for MM. Prophylactic measures in patients with preexisting-kidney failure may further reduce this risk., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Defined as a rare extramedullary tumor, myeloid sarcoma (MS) is in the attention of specialists, although the information in the literature is represented especially through case reports. MS can precede acute myeloid leukemia (AML), appear simultaneous and can be the only manifestation of leukemia relapse after allogeneic stem cell transplantation (allo-SCT). We present the case of a 30-year-old female diagnosed with acute myelomonocytic leukemia (AML M4), with complete remission (CR) after chemotherapy, followed by allo-SCT for consolidation. After five months, the patient presented right breast tumors. Ultrasound-guided biopsy of the breast lesion displayed diffuse infiltration of undifferentiated tumor cells, with blastic granulocytic features, strongly immunopositive for cluster of differentiation (CD) 45, CD99, CD34 and myeloperoxidase (MPO) and negative for all epithelial markers [MNF116, cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), E-cadherin]. The final diagnosis was AML relapse with breast MS. After multiple leukemia relapses with breast MS, the patient died with cerebral bleeding secondary to severe thrombocytopenia.

The proportion of patients with hematological malignancies (HM) who develop rare invasive fungal infections (IFI) has increased worldwide over the past few decades. Zygomycosis is an opportunistic fungal infection, which begins in the nose and paranasal sinuses due to inhalation of fungal spores. Rhino-cerebral zygomycosis is the most common form of the disease, it typically develops in diabetic or immunocompromised patients and presents as an acute fulminate infection, which is often lethal. We report a case of rhino-cerebral zygomycosis in an allotransplanted patient to emphasize early diagnosis and treatment of this potentially fatal fungal infection. We discuss different risk factors, specific diagnosis procedures and review the current concepts in management of zygomycosis.