Diagnosis and treatment of spinal myeloid sarcoma with acute spinal cord compression as an initial symptom: a report of 5 cases

Epidural chloroma and spinal cord compression

Objective To observe the efficacy of maintenance treatment with decitabine and dasatinib after allogenic hematopoietic stem cell transplantation for myeloid sarcoma. Methods A 29-year-old male patient was diagnosed with abdominal myeloid sarcoma and acute myeloid leukemia with c-kit mutation and t(8; 21). Allogeneic hematopoietic stem cell transplantation was performed after inducted remission. The conditioning regimen was decitabine + FLAG + modified Bu/Cy. Prophylaxis of GVHD was performed with cyclosporine mycophenolate mofetil and short-term methotrexate. The patient received 11.73×108 mononucleated cells/kg and 17.59×106CD34+ cells/kg from donor. At Day 13 post-transplantation, neutrophils reached 0.5×109/L and platelet count was 20×109/L. Decitabine was prescribed since Day 50 post-transplantation monthly for 5 courses. And dasatinib was offered orally since Day 100 for 4 months. Results It was followed up to 16 months post-transplantation. There were no obvious abnormalities of bone marrow cytology, AML/ETO fusion gene quantification, cerebrospinal fluid or abdominal enhanced computed tomography (CT). Conclusions Hematopoietic stem cell transplantation is an effective treatment for myeloid sarcoma. Decitabine has some efficacy for myeloid sarcoma and it may be used for maintenance treatment after transplantation. Tyrosine kinase inhibitors reduce recurrence in myeloid sarcoma with c-kit mutation. The treatment of decitabine and dasatinib after allogeneic hematopoietic stem cell transplantation yield excellent outcomes. This is the first report in domestic and foreign literatures. Key words: Hematopoietic stem cell transplantation; Myeloid sarcoma; Allogene

Spinal Cord Compression in Patients with Acute Myeloid and Lymphoid Leukemia

Objective To investigate the clinical characteristics, curative effect and prognosis of myeloid sarcoma. Methods The clinical data of 12 patients with MS diagnosed at Xijing Hospital of Air Force Medical University from August 2008 to May 2018 were retrospectively analyzed. Their clinical manifestations, diagnosis, treatment and survival were analyzed. Results Twelve patients were 17 to 62 years old. The initial site included lymph node, external auditory canal, eye, buttock, lung, liver, pancreas, breast, skin, vertebra and its surroundings,and cervix. Among 11 patients with peripheral blood classification, bone marrow aspiration and bone marrow biopsy, 6 cases were isolated MS [one of which developed acute myeloid leukemia (AML)], 1 case was chronic myeloid leukemia in chronic phase, 2 cases were AML-M2, and 1 case was myelodysplastic syndrome (MDS), and 1 case was after aplastic anemia (AA) with no infiltration of bone marrow. Immunohistochemical results showed that LCA(+) (7/7), MPO(+) (12/12), CD43(+) (9/9), lysozyme(+) (5/7), CD3(-) (8/8), CD20(-) (9/9), CD34(+) (5/6), CD117(+) (7/7), and Ki-67(+) 30%-90%. Four patients were examined for bone marrow chromosomes, 2 patients with AML had t(8;21), 1 patient with MDS was 47, XX, +8, del(11)(q21), and 1 patient with CML was t(9;22). Two of the 12 patients were lost to follow-up. Among the 10 patients who were followed up, 6 died and 4 survived, and the median survival time was 21 months (2-27 months). Conclusions AA in stable phase with MS and CML in chronic phase with MS are rarely reported. The clinical manifestations of MS patients are varied, of which the common incidence sites are superficial lymph nodes, the infrequent sites are vertebra and its surrounding areas, and the rare sites are eye, pancreas, lung, liver, etc. The median survival time of MS patient is short and the curative effect is poor. Key words: Sarcoma, myeloid; Leukemia, myeloid, acute; Leukemia, myelogenous, chronic; Anemia, aplastic

Objective To evaluate the efficacy of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in patients with myeloid sarcoma (MS). Methods The therapeutic effect of allo-HSCT on 16 patients with MS in our center was retrospectively analyzed. Among them, 5 patients were diagnosed as isolated MS, 10 patients were MS presenting with acute myeloid leukemia(AML)and 1 was accompanied with myelodysplastic syndrome/myeloproliferative neoplasm(MDS/MPN). Results All of the 16 patients were diagnosed as MS by pathological biopsies. Patients were initially treated with chemotherapy and then allo-HSCT. Hematopoiesis reconstitution was achieved in all the patients, with a median follow-up time of 36(4-106)months after transplantation, 7 patients died. The 3-year overall survival(OS) was 54.17%. Six patients(37.5%)relapsed after allo-HSCT, and the relapse was the major cause of death. Conclusions Allo-HSCT is an effective therapeutic option for patients with MS. Key words: Allogeneic hematopoietic stem cell transplantation; Myeloid sarcoma; Outcome

Minimal Residual Disease following Allogeneic Hematopoietic Stem Cell Transplantation

Spinal cord compression secondary to spinal extradural myeloid sarcoma in acute myeloid leukaemia: A case report and literature review

Context: Granulocytic sarcoma (GS) is an extramedullary form of proliferating myeloblasts. It is frequently reported in patients with acute myeloid leukemia (AML) but rarely in patients with chronic myeloid leukemia (CML). Spinal cord compression caused by CML-associated GS is exceedingly rare, with only few cases reported in the literature. To our knowledge, this is the first reported case in which GS caused such extensive compression. Findings: A 37-year-old man with CML suffered from back pain for 2 months. Notably, he had already achieved molecular remission (MR) after receiving imatinib mesylate for CML; bone marrow aspiration results were consistent with CML in chronic phase. Image examination revealed that developed GS occupied nearly the entire thoracic spinal canal, thereby causing extensive spinal cord compression. The tumor completely diminished after his treatment regimen was upgraded. He showed no signs of recurrence after 1-year follow-up. Conclusion: Extramedullary infiltration of CML should be taken into consideration when a mass lesion develops and compresses the spinal cord in a CML patient who has been receiving routine and standard treatment modalities; thus, a sudden and unexpected progression mandates a refinement and upgrade of treatment modality.

Objective To strengthen the understanding of granulocytic sarcomas (GS) by investigating the clinical characteristics of GS of spine. Methods The clinical data of 2 GS patients were retrospectively analyzed, and the related literature was reviewed. Results Because of the double lower limbs numbness, the 2 GS patients came to orthopedics department of the 306th Hospital of PLA. Magnetic resonance imaging (MRI) of the 2 patients showed an epidural mass located at the 9th-11th and 2nd-4th thoracic levels. Their histopathological examination and immunohistochemistry revealed GS. For example 1, she was diagnosed with acute promyelocytic leukemia (APL) and has been morphologic complete commission (CR) from 1995 to 2015. Chemotherapy and all-trans retinoic acid (ATRA) were performed after extramedullary relapse in thoracic spine, breast, ovary, sternum bone and lymph nodes. So far, the patient is still in follow-up. For example 2, he was diagnosed as isolated GS by morphology, immune phenotype, chromosome and gene examinations. Because he refused chemotherapy, radiotherapy was performed after surgical intervention. So far, he is loss of follow-up. Conclusions Spinal epidural of GS is rare. Surgery can reduce or remove nerve compression symptoms, and help clear diagnosis. The current recommended treatment regimen in patients presenting with isolated GS or GS presenting concomitantly with AML is conventional AML-type chemotherapeutic protocols. The differences in prognosis of GS patients may be partially attributed to different characteristics of patient. Key words: Sarcoma, myeloid; Leukemia, promyelocytic, acute; Spinal cord compression; Spinal canal; Thoracic vertebrae

Multiple myeloma presenting with acute bony spinal cord compression and mechanical instability successfully managed nonoperatively

Single-center experience with mitoxantrone hydrochloride liposome-based therapy for patients with myeloid sarcoma

Background: Myeloid sarcoma (MS) is a malignant extramedullary tumor that occurs in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). The standard first-line treatment for MS is intensive chemotherapy according to the AML protocol, regardless of bone marrow involvement. The role of allogeneic hematopoietic stem cell transplantation (alloHSCT) in the treatment of pediatric patients with MS requires further investigation. The aim of the study was to evaluate treatment outcomes for MS in pediatric patients with a focus on assessing the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on treatment efficacy. Material and Methods: The study included 64 patients aged 0 to 19 years from 15 pediatric oncology centers in Poland who were diagnosed with MS between 1998 and 2024. An Excel database was created to collect data on clinical features and treatment methods and outcomes. Results: The probability of 5-year overall survival (pOS) for the entire cohort was 0.63 ± 0.07, while the 5-year event-free survival (pEFS) and 5-year relapse-free survival (pRFS) were 0.62 ± 0.07 and 0.72 ± 0.07, respectively. Treatment outcomes were compared between patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) in first complete remission (ICR) (n1 = 17/64; 27%) and those who did not receive alloHSCT (n2 = 47/64; 73%). In the alloHSCT group (n1), the estimated survival probabilities were pOS = 0.49 ± 0.13, pEFS = 0.44 ± 0.14, and pRFS = 0.40 ± 0.14. In the non-alloHSCT group (n2), these values were pOS = 0.68 ± 0.08, pEFS = 0.68 ± 0.08, and pRFS = 0.84 ± 0.06. The difference in pRFS between groups n1 and n2 was statistically significant (p = 0.0049). Extramedullary relapses were more frequently observed in patients who had undergone allogeneic hematopoietic stem cell transplantation (alloHSCT) (p = 0.0001). Conclusions: Allogeneic hematopoietic stem cell transplantation (alloHSCT) does not improve the outcome of patients with MS. Further research is needed to identify effective strategies for sustaining remission in patients with MS after alloHSCT.

Dear Editor, In April 2009, a 19-year-old male presented with progressive pain on his left upper arm. A MRI scan of the arm showed a large tumor of the distal left humerus (Fig. 1a). Because an osteosarcoma was suspected, a biopsy was performed. After the biopsy, the patient presented with a fracture of his arm as a result of minor trauma. This fracture was managed conservatively with an upper arm cast. The biopsy revealed necrotic bone fragments with an infiltration of myeloblasts admixed with immature eosinophils; hence, the diagnosis of a myeloid sarcoma (MS) was established. Besides the pain in his arm, the patient had no complaints, especially no fever, night sweats, weight loss, hemorrhage, or anemia. On physical examination, neither lymphadenopathy and hepatosplenomegaly nor neurological signs were noticed. His peripheral blood counts were normal. A PET scan did not show any other bone lesion. On histological examination, the MS consisted of myelo/monoblasts with expression of lysozyme, partly weak myeloid peroxidase (MPO), and focally CD34 and CD117. A bone marrow aspirate was performed to exclude acute myeloid leukemia (AML). Morphology of the bone marrow did not support a diagnosis of AML or chronic myeloid leukemia (CML), although with flow cytometric immunophenotyping (IPT), a small population (2 %) of aberrant myeloblasts expressing CD15, CD34, and CD117 were found. Intriguingly, cytogenetic analysis of the bone marrow aspirate showed a Philadelphia chromosome (t(9;22)(q34;q11.2)) in 2 of 13 analyzed cells. Subsequent fluorescence in situ hybridization on the tumor biopsy showed that the blasts harbored the BCR-ABL fusion gene (Fig. 1b). PCR performed on peripheral blood and bone marrow showed BCR-ABL levels of 3.3×10 and 1.5×10 copies/ml, respectively. Because of the bad prognosis, the patient was treated with intensive chemotherapy followed by allogeneic stem cell transplantation (SCT) with peripheral blood stem cells from a matched unrelated donor. The therapy was complemented with local radiotherapy of his left arm. During his treatment, the left arm recovered swiftly, and at the time of SCT, he was no longer depending on the cast. Now 2 years after SCT, he is still in remission with an undetectable BCR-ABL level. MS is a rare disease that is reported in 2.5–9.0 % of patients with AML. It can occur concomitantly, following or, rarely, antedating the onset of systemic AML [1]. MS can also occur in the presence of other hematological diseases such as myelodysplastic syndrome and myeloproliferative neoplasia, including CML [2]. Certain known cytogenetic abnormalities, in particular t(8;21), have been associated with a higher incidence of MS [1, 2]. However, the presence of a Philadelphia chromosome t(9;22) is extremely rare and virtually no reports exist on cases in AML with the remainder almost exclusively occurring during CML blast crisis [2]. The phenotype of MS is mostly monoblastic or myelomonocytic, often expressing CD34, CD68, CD99, CD117, MPO, and TdT [2]. In our patient, the MS had this common L. F. J. van Groningen (*) :W. J. F. M. van der Velden Department of Hematology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands e-mail: l.vangroningen@aig.umcn.nl

Myeloid sarcoma is a rare hematological neoplasm that may develop de novo or concurrently with acute myeloid leukemia (AML), or represent the initial manifestation of relapse in a previously treated AML in remission. A 44-year-old man was diagnosed with testis MS in his local hospital. A month later, November 2010, our department confirmed the clinical diagnosis of AML through his bone marrow biopsy and aspirate. The patient underwent allogeneic hematological stem cell transplantation from his sister and achieved complete remission. Five months later, however, a mass in his adrenal was revealed by Positron Emission Tomography-Computer Tomography (PET-CT). After a multidisciplinary team diagnosis, radiotherapy for this lesion was performed. As of the follow up conducted until March 2013, the patient remains healthy and shows no evidence of recurrent MS or leukemia.

Introduction/Objective Extramedullary involvement by myeloid precursor cells - known as myeloid sarcoma -is a well-recognized manifestation of myeloid neoplasms, typically resulting from leukemic cells migrating through circulation and infiltrating peripheral tissues. In contrast, histiocytic lesions associated with myeloid neoplasms are rare and have been less extensively explored. The WHO reports a 3-15% prevalence of mature myeloid neoplasms in patients with Erdheim-Chester Disease (ECD), a rare non-Langerhans cell histiocytosis. Histiocytic neoplasms—including Langerhans cell histiocytosis and ECD—are frequently driven by activating mutations in the mitogen-activated protein kinase (MAPK) signaling pathway, most commonly involving BRAF, NRAS, KRAS, or MAP2K1. These mutations are thought to promote clonal proliferation and survival of histiocytic-lineage cells. Emerging evidence suggests at least a subset of histiocytic proliferations may arise from a shared hematopoietic progenitor clone, supporting a clonal relationship with underlying myeloid malignancies. A recent study further strengthened this link by identifying shared mutations—most commonly ASXL1, TET2, and SRSF2—between cutaneous histiocytic-dendritic lesions and underlying myeloid neoplasms. Here, we present a novel case of non-Langerhans cell histiocytic lesions arising after allogeneic hematopoietic stem cell transplantation (HSCT) in a patient with acute myeloid leukemia (AML), demonstrating overlapping cytogenetic and molecular features that support a clonal relationship. Methods/Case Report A 64-year-old male with no significant medical history presented with febrile neutropenia. Bone marrow biopsy revealed 35% blasts with an immunophenotype consistent with AML. Cytogenetic studies showed trisomy 8, and next-generation sequencing (NGS) detected ASXL1, DNMT3A (x2), and IDH2 mutations -meeting criteria for AML with myelodysplasia-related changes. The patient was treated with decitabine and venetoclax. Follow-up bone marrow biopsies demonstrated morphologic remission of AML; however, persistent dyserythropoiesis, ring sideroblasts, atypical megakaryocytic hyperplasia, and continued evidence of trisomy 8 were noted. He subsequently underwent allogeneic HSCT. Post-transplant marrow evaluation revealed complete remission with normal cytogenetics, resolution of dysplasia, and no detectable mutations on myeloid NGS panel. Six months post-transplant, the patient developed facial papules and mucosal lesions involving the oral cavity and trachea. Biopsy revealed xanthogranulomatous inflammation characterized by foamy macrophages and multinucleated giant cells. Immunohistochemistry was positive for CD68, CD163, and cyclin D1, and negative for Langerin, CD1a, S100, ALK, and BRAF V600E. Recurrence of these lesions, including new lung nodules, prompted repeat biopsies which confirmed similar non-Langerhans cell histiocytic lesions. Ancillary testing demonstrated the same cytogenetic and mutational profile as the original AML with one additional finding -a CDKN1B mutation. Results NA Conclusion Following allogeneic hematopoietic stem cell transplantation (HSCT), the patient developed cutaneous, mucosal, and pulmonary non-Langerhans cell histiocytic lesions that shared cytogenetic and molecular features with the original AML. A CDKN1B mutation was also identified, along with aberrant cyclin D1 expression within the histiocytic proliferation. CDKN1B is not typically associated with histiocytic neoplasms -which more commonly harbor MAPK pathway mutations (e.g., BRAF, NRAS, KRAS, MAP2K1) -all of which were absent in this case. These findings further support the possibility of clonal evolution or transdifferentiation from a common progenitor shared with the antecedent myeloid malignancy. While this case exhibits clinical and histologic features reminiscent of Erdheim-Chester disease, the absence of MAPK pathway mutations is unusual. The molecular profile is more consistent with a clonal histiocytic proliferation arising from a myeloid progenitor. Furthermore, although non-Langerhans cell histiocytic lesions have been described in the setting of MDS, MPNs, and overlap syndromes, to our knowledge, this is the first reported case arising post-transplant in AML. The presence of an ASXL1 mutation in both the AML and the histiocytic lesion is notable, as this gene is recurrently mutated in previously reported cases of clonal histiocytic-dendritic proliferations arising from myeloid neoplasms.