Lymphoma-associated hemophagocytic lymphohistiocytosis: experience in adults from a single institution

Yu, Jeffrey; Wang, Chenyu; Yang, Youngsen; Wang, Ren‐Ching; Chang, Kuang-Hsi; Hwang, Wen-Li; Teng, Chieh‐Lin Jerry

doi:10.1007/s00277-013-1784-3

Cited by 70 publications

(52 citation statements)

References 24 publications

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“…[9][10][11] The incidence and mortality of HLH in T-cell lymphoma is especially high. 5 No malignancy or other cause was identified in patients 3 and 6, despite multiple investigations that were performed.…”

Section: Patient Characteristics and Laboratory Findingsmentioning

confidence: 99%

Secondary hemophagocytic lymphohistiocytosis in adults: a case series of 6 patients in a single institution in a brief period

Alwaheed¹,

Maraj²,

Mykytiv³

et al. 2018

HTIJ

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We present a case series of 5 patients of secondary hemophagocytic lympohistiocytosis (HLH) in a single institution in relatively brief period. HLH is uncommon, but it also tends to be under diagnosed, especially if it is secondary to other haematological or non-haematological malignancy. The diagnosis is challenging and is frequently delayed. Stem cell transplantation is a potentially curative option however; it is not suitable for most patients because of age and performance status or the inability to achieve complete remission prior to transplantation. In our experience, the disease was always refractory, and the outcome was poor, regardless of the treatment that was used.Keywords: hemophagocytic lymphohistiocytosis, fever of unknown origin,

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Section: Patient Characteristics and Laboratory Findingsmentioning

confidence: 99%

Secondary hemophagocytic lymphohistiocytosis in adults: a case series of 6 patients in a single institution in a brief period

Alwaheed¹,

Maraj²,

Mykytiv³

et al. 2018

HTIJ

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“…The overall mortality associated with malignancy-associated HLH is .90%, and chemotherapy may not salvage these patients because of endorgan dysfunction at presentation. 92,93 Treatment of lymphomaassociated HLH (LA-HLH) involves HLH-94/HLH-2004 protocol and treating the underlying B-or T-cell lymphoma with chemotherapy. The majority of B-cell lymphoma-related HLH was DLBCL and treatment consisted of rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone.…”

Section: Treatmentmentioning

confidence: 99%

Proliferation through activation: hemophagocytic lymphohistiocytosis in hematologic malignancy

Vick¹,

Patel

Prouet

et al. 2017

Blood Advances

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Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of cytokine-driven immune activation. Cardinal features include fever, hemophagocytosis, hepatosplenomegaly, lymphocytic infiltration, and hypercytokinemia that result in multisystem organ dysfunction and failure. Familial HLH is genetically driven, whereas secondary HLH (SHL) is caused by drugs, autoimmune disease, infection, or cancer. SHL is associated with worse outcomes, with a median overall survival typically of less than 1 year. This reflects difficulty in both diagnostic accuracy and in establishing reliable treatments, especially in cases of malignancyinduced SHL, which have significantly worse outcomes. Malignancy-induced HLH is seen almost exclusively with hematologic malignancies, constituting 97% of cases in the literature over the past 2 years. In these situations, the native immune response driven by CD8 T cells produces an overabundance of T helper 1 cytokines, notably interferon-g, tumor necrosis factor-a, and interleukin-6, which establish a positive feedback loop of inflammation, enhancing replication of hematologic malignancies while leaving the host immune system in disarray. In this paper, we present 2 case studies of secondary HLH driven by HM, followed by a review of the literature discussing the cytokines driving HLH, diagnostic criteria, and current treatments used or undergoing investigation. Case 1A previously healthy 34-year-old male presented with progressive malaise, fevers, and abdominal discomfort. He was found to have massive splenomegaly along with pancytopenia and coagulopathy. Initial laboratory studies showed lactate dehydrogenase (LDH) 470 U/L, ferritin 4450 ng/dL, white blood cell count 1.3 3 10 9 /L, platelets 31 3 10 9 /L, hematocrit 22%, and fibrinogen level 130 mg/dL. A bone marrow (BM) biopsy was performed and showed lymphohistiocytic aggregation without hemophagocytosis. The patient underwent splenectomy; pathology showed splenic red pulp congestion and proliferation of sheets of normal histiocytes with marked erythrophagocytosis. No conclusive evidence of B-or T-cell lymphoma was found at that time, although features suggestive of but not diagnostic for T-cell rich diffuse large B-cell lymphoma (DLBCL) were seen in the spleen. The patient subsequently had a positron emission tomography/computed tomography scan and was found to have small hyperactive para-aortic lymph nodes that were not accessible for biopsy. The patient began therapy for HLH with dexamethasone and etoposide for 6 cycles and tolerated it well, with resolution of his laboratory abnormalities and symptoms.A year and a half after initial diagnosis, he presented to the hospital again with back pain and fevers. A computed tomography scan showed multiple retroperitoneal and periaortic lymph nodes along with liver lesions. He was started on dexamethasone and admitted to the hospital. Multiple lymph node biopsies were performed and were inconclusive, possibly from steroid pretreatment. Further evaluation with bilateral BM biopsies reported T-cell rich ...

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“…For adults, transplantation using two cord units is frequently necessary [3][4][5] and literature demonstrates that double umbilical cord blood transplantation (DUCT) yields durable remissions [1,5,6]. Data on DUCT in hepatosplenic gamma-delta T-cell lymphoma with hemophagocytic lymphohistiocytosis (HLH) are limited to case reports [7,8]. We describe a 22-year-old woman with hepatosplenic gamma-delta lymphoma with hemophagocytosis treated with DUCT.…”

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confidence: 99%

Umbilical cord blood transplantation induces a durable remission in hepatosplenic gamma‐delta T cell lymphoma with associated hemophagocytic lymphohistiocytosis

2014

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Thirty patients (88%) died, with a median OS of 4.5 months (95%CI 2.6-8.6) and a 3-year OS of 18% (95%CI 7-32). Cause of death was disease relapse/progression in 23 cases (77%), while the remaining 7 (23%) died of nonrelapse mortality (NRM). Twenty-nine patients were evaluable for response after SCT, as five died of early NRM. Nineteen patients (66%) achieved CR: 13/19 (68%) relapsed after a median of 3.4 months (range 1.7-18.2) and survived for a further 1.4 months (range 0.4-9); among the six patients in sustained CR, four are alive and two died of NRM after 79 and 55 months. Ten patients (34%) had resistant leukemia after SCT and died in a median of 2.5 months (range, 1.4-6.6).Considering pretransplant characteristics, OS was not predicted by gender, karyotype, age at SCT, time to SCT, number of chemotherapy courses, donor type, stem cell source, or conditioning regimen. There was a significant association between OS and WBC count at SCT (<10,000/ml: 20 months [95%CI 4.6-NA] vs. 10,000/ml: 3.6 months [95%CI 1.9-4.5], P < 0.0001), platelet (PLT) count at SCT (>30,000/ml: 18.8 months [95%CI 3.6-NA] vs. 30,000/ml: 3.7 months [95%C 1.9-10], P 5 0.05) and PB blasts at SCT (absent: 79 months [95%CI 2.6-NA] vs. present: 4.5 months [95%CI 3.4-8.6], P 5 0.03). Stratifying patients according to WBC, PLT, and circulating blasts, we identified four groups with different survival: median OS for patients with 0, 1, 2, or 3 adverse prognostic factors was 79, 10.1, 4.1, and 3.5 months, respectively (P 5 0.004) (Fig. 1).Our data confirm that allogeneic SCT can cure a minority of patients with primary refractory AML, and that relapse is the major cause of treatment failure after SCT. In our experience, 3-year OS was lower than that of the MDACC group (18% compared to 39%) but comparable to that reported by the GITMO (10%) [2] and significantly superior to survival after salvage chemotherapy (2-5%) [1,3]. Jabbour et al. found higher WBC, lower PLT, and higher BM blasts percentage at SCT to be associated with superior OS, but did not define any cutoff value [1]. In the setting of unrelated donor transplant for AML primary refractory to various induction strategies (conventional 3 1 7 or HDACbased regimens), Craddock et al. identified number of chemotherapy courses before SCT (>2) and BM blasts percentage (above a median of 38.5%), along with patient CMV serostatus, as predictive factors for OS [4]. We found that WBC count <10,000/ml, PLT count >30,000/ml and absence of circulating blasts predict superior long-term outcome after SCT. If confirmed in larger studies, this finding may help in designing a simple pre-SCT score to identify AML patients primary refractory to intensive induction chemotherapy that could maximally benefit from the transplant procedure.

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Lymphoma-associated hemophagocytic lymphohistiocytosis: experience in adults from a single institution

Cited by 70 publications

References 24 publications

Secondary hemophagocytic lymphohistiocytosis in adults: a case series of 6 patients in a single institution in a brief period

Secondary hemophagocytic lymphohistiocytosis in adults: a case series of 6 patients in a single institution in a brief period

Proliferation through activation: hemophagocytic lymphohistiocytosis in hematologic malignancy

Umbilical cord blood transplantation induces a durable remission in hepatosplenic gamma‐delta T cell lymphoma with associated hemophagocytic lymphohistiocytosis

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