IACH NEWS OF THE WEEK

June 17, 2026
Prepared by Dr Edwin Uriel Suárez

POEMS Syndrome: 2026 Update on Diagnosis, Risk-Stratification, and Management (AJH Review - "ANNUAL CLINICAL UPDATES IN HEMATOLOGICAL MALIGNANCIES")

Key points:

-        There are three important points that relate to this memorable acronym POEMS (polyneuropathy, organomegaly, endrocrinopathy, monoclonal plasma cell disorder [PCD], skin changes):

(1) Not all of the features within the acronym are required to make the diagnosis.

(2) There are other important features not included in the POEMS acronym, including papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis/erythrocytosis (P.E.S.T.), elevated levels of vascular endothelial growth factor (VEGF), a predisposition towards thrombosis, and abnormal pulmonary function tests.

(3) There is a Castleman disease variant of POEMS syndrome that is associated with a clonal PCD. Other names of the POEMS syndrome that are less frequently used are osteosclerotic myeloma, Takatsuki syndrome or Crow-Fukase syndrome.

-        POEMS syndrome is a rare life-threatening syndrome due to an underlying PCD. The major criteria for the syndrome are polyneuropathy, clonal PCD, sclerotic bone lesions, elevated VEGF, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis.

-        The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyneuropathy and clonal PCD (almost always λ), and at least one of the minor criteria.

-        Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced estimated glomerular filtration rate.

-        The introduction of mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings. Moreover, it would prevent misdiagnosis, reducing morbidity and the cost associated with delayed diagnosis.

-        For those patients with a dominant plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement should receive systemic therapy. Corticosteroids are temporizing, but alkylators and lenalidomide are the mainstays of treatment, the former either in the form of low dose conventional therapy or as high-dose conditioning for stem cell transplantation. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Daratumumab combinations also appear promising based on case series. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. 

Autologous and allogeneic haematopoietic cell transplantation in adult patients with Hodgkin lymphoma: recommendations from the EBMT Practice Harmonisation and Guidelines Committee and Lymphoma Working Party 

 Key points: See Table 1 and Table 2 in original paper.

1. Autologous hematopoietic cell transplantation (HCT)

-        Which patients are candidates for autologous HCT?: Refractory or relapsed patients in advanced stage and sensitive disease after salvage therapy. For patients with early-stage disease and abbreviated previous therapy, treatment with chemotherapy with or without brentuximab vedotin or checkpoint inhibitors with or without radiotherapy can be considered.

-        What is the optimal salvage therapy regimen before autologous HCT?: Brentuximab vedotin or checkpoint inhibitors to be included in salvage therapy. The decision between brentuximab vedotin, checkpoint inhibitors or both will depend on: previous treatments received, disease stage and tumour bulk at relapse, and time to relapse.

-        Is reaching a metabolic complete remission (mCR) essential before proceeding with autologous HCT?: mCR should be attempted to be reached before autologous HCT using salvage chemotherapy with or without new drugs (including brentuximab vedotin and checkpoint inhibitors). Autologous HCT is recommended in patients with partial response with low-volume disease if they received brentuximab vedotin and checkpoint inhibitors as part of salvage regimen.

-        What is the role of radiotherapy before or after autologous HCT?: When considered, early consultation with a radiation oncologist is recommended; radiotherapy to positron emission tomography-positive (PET+) lesions before autologous HCT could be considered; radiotherapy can be considered for patients with persistent PET+ lesions after autologous HCT. Radiotherapy including a clinically significant dose to the lungs should be used cautiously.

-        What is the optimal conditioning regimen before autologous HCT?: No prospective randomised trials indicate the superiority of any preparatory regimen; however, BEAM (BCNU [carmustine], etoposide, cytarabine and melphalan) is the most frequently used conditioning regimen. In the case of shortage of BCNU, LEAM (as BEAM but replacing BCNU with CCNU [lomustine]) or thiotepa (5–7 mg/kg maximum) are an option.

-        Which patients should receive consolidation after autologous HCT?: Brentuximab vedotin consolidation in brentuximab vedotin-naive patients with classical Hodgkin lymphoma (HL) without complete remission pre-transplantation and/or with one or more high-risk factor (following the AETHERA trial); off-label checkpoint inhibitor consolidation (eg, pembrolizumab and nivolumab) can be considered in patients with classical HL with high-risk factors and brentuximab vedotin-refractory disease or brentuximab vedotin-intolerance; off-label consolidation with brentuximab vedotin and checkpoint inhibitors can be considered in patients who are not refractory and not intolerant to brentuximab vedotin.

-        Brentuximab vedotin consolidation in patients with classical HL with one or more high-risk factor and minimal previous vedotin exposure (1–6 cycles), provided no brentuximab vedotin-refractoriness and no previous neurotoxicity; the benefit of checkpoint inhibitors should be weighed against potential immune-related side-effects; radiotherapy can be considered for patients with persistent PET+ lesions after autologous HCT.

2. Allogeneic HCT

-        Which patients with HL are candidates for allogeneic HCT?: Consolidation with allogeneic HCT is recommended for eligible patients, post-brentuximab vedotin and post-checkpoint inhibitor exposure (eligibility defined as relapse after autologous HCT, adequate organ function and physical condition, and sensitive disease before allogeneic HCT); for refractory patients, decision to allograft should be made on an individual basis; time interval between the last dose of checkpoint inhibitor and allogeneic HCT is preferably at least 6 weeks if clinically feasible; consider the use of bridging therapy before allogeneic HCT to reduce the risk of relapse.

-        Allogeneic HCT can be postponed in patients with complete remission post-checkpoint inhibitor as many of these patients can reach long-lasting remission and some may possibly be cured.

-        Donor selection. In order of preference: human leukocyte antigen (HLA)-matched sibling donor, HLA-matched unrelated donor, and HLA-haploidentical donor or HLA-mismatched unrelated donor. Cord blood should be avoided in adults except if no alternative donor is available.

-        Conditioning regimen: Reduced intensity conditioning (such as Flu-Mel, FB2, or FC-TBI) are preferred; in patients with high relapse risk, conditioning regimens with higher intensity (but reduced organ toxicity) may be considered (eg, T1B2F); BEAM-based conditioning could be considered in allogeneic HCT as a first transplant.

-        Graft-versus-host disease (GVHD) prophylaxis: post-transplant cyclophosphamide is the recommended GVHD prophylaxis independently of the donor (particularly in checkpoint inhibitor pre-treated patients). Other methods of T-cell depletion, such as antithymocyte globulin or alemtuzumab plus donor lymphocyte infusion (DLI), could be considered for HLA-identical siblings or unrelated donors.

-        How to prevent and manage relapse after allogeneic HCT?: There is no recommendation for maintenance therapy after allogeneic HCT outside of clinical trials; clinical trials and new biomarkers should be developed to make a recommendation on maintenance therapy; treatment of relapse should include the following: rapid tapering of immunosuppression, DLI with or without brentuximab vedotin (checkpoint inhibitors should be used with caution), chemotherapy, brentuximab vedotin, checkpoint inhibitors with caution, and radiotherapy, as well as more prospective clinical trials including trials on cellular therapy. Radiotherapy can be considered for patients with persistent PET+ lesions after allogeneic HCT. 

Diagnosis and management of neutropenia in adults: Expert guidance

Key points:

-        Neutropenia in general is defined as a blood neutrophil count of less than 1.5×10⁹/L,  in severe neutropenia counts drop to less than 0.5×10⁹/L, but the definition of neutropenia varies according to the patient's ethnic origin and age.

-        For Caucasian adults, the absolute neutrophil count (ANC) threshold of 1.8×10⁹/L is adopted for the definition of neutropenia according to the World Health Organization.

-        It can be inherited or acquired, and it is an uncommon haematological finding in adult outpatient clinics. Neutropenia can result from decreased production of neutrophil precursors in the bone marrow, as in the case of severe congenital neutropenia, or from increased utilization of neutrophils in some bacterial infections, or accelerated  destruction as is the case with drug-induced neutropenia, viral infections and autoimmune neutropenia. See Figure 3 in original paper: "Flowchart for the basic evaluation of a patient with chronic neutropenia".

-        Cyclic neutropenia (CyN) is characterized by oscillating numbers of blood neutrophils, monocytes, platelets, reticulocytes and lymphocytes, usually with a 21- day periodicity. Mutations in ELANE (Neutrophil Elastase) can cause cyclic  neutropenia and, although there is some overlap in ELANE  mutations with congenital neutropenia, genotype–phenotype correlations indicate  that there are mutations that are more likely to be associated with CyN.

-        It should be noted that some individuals of African and  Middle Eastern descent display normal ANCs in the range  from 0.5 to 1.5×10⁹/L and less frequently even lower. The term atypical chemokine receptor (ACKR1/DARC)-associated neutropenia, instead of ethnic neutropenia, is now used to emphasize the genetic rather than the ethnic basis of this entity.

-        Severe chronic neutropenia (SCN) in adults is usually encountered in one of three situations:

●      Routine blood count of ANC <0.5×10⁹, with or without other haematological findings;

●      Recurrent fevers, pharyngitis, sinusitis, otitis, stomatitis or respiratory infections which may be slow to resolve;

●      Family history of SCN caused by a germline mutation.

-        Adults with chronic idiopathic neutropenia are not expected to evolve to another autoimmune disorder or to develop myelodysplastic syndrome or acute myeloid leukemia. If patients require granulocyte colony-stimulating factor (G-CSF), they can be  expected to stay on the same low dose of G-CSF for many  years.

-        Symptomatic patients with drug-induced neutropenia usually present with fever, myalgia and sore throat but usually no rash or evidence of allergy elsewhere. Blood examination shows few or absent neutrophils. Mild lymphopenia may be observed, but other cell counts are usually normal. Treatment usually consists of supportive care, including broad-spectrum antibiotics for febrile patients. Haematopoietic growth factors may be beneficial, but their use in this setting has not been established in randomized trials.

-        Treatment with rituximab can also cause a late-onset  neutropenia (LON). LON typically occurs at least  4 weeks after the last dose of rituximab, most commonly  between 4 and 12 weeks, but sometimes it may take several  months to appear. LON is often transient but can reach  severe levels (neutrophils <500/μL). The pathophysiology of LON is multifactorial and not fully understood.

-        Adult patients with a careful medical history indicative of acquired neutropenia, that is, a healthy childhood without recurrent fevers or infections, may have an autoimmune  disorder not recognizable through testing for anti-neutrophil antibodies. Their cytopenia is selective; other blood cell counts are normal or near normal. The results of the bone marrow morphology tests and other tests, including the anti-nuclear antibody tests are normal. In general, therapy should be  conservative and expectant. Intravenous γ-globulin may transiently increase neutrophils, but the therapy is expensive and  relatively ineffective. The response to glucocorticoid therapy is unpredictable. Daily or alternate-day G-CSF is effective but should be reserved for patients with recurrent infections.

-        SCN increases susceptibility to bacterial  or fungal infections. Treating severe chronic neutropenia patients with G-CSF can increase neutrophil counts for most types of  neutropenia. 

Immunodeficiency-associated primary CNS  lymphomas: an International Primary CNS Lymphoma Collaborative Group study (Retrospective study)

Highlights:

• Rituximab and  methotrexate–based  chemotherapy was  associated with highest

response rates and  prolonged progression free survival (PFS) in immunodeficiency-associated primary central nervous system  lymphoma (ID-PCNSL).

• The newly developed  International Primary CNS Lymphoma

Collaborative Group (IPCG) prognostic score  for ID-PCNSL integrates age, Karnofsky performance status (KPS), Epstein-Barr virus (EBV) status and allows improved prognostic stratification of ID-PCNSL.

ID-PCNSL represents a clinicopathologically distinct PCNSL subtype, for which large studies and  prognostic models are lacking. To address this gap, the International PCNSL Collaborative Group conducted a retrospective multicenter study on 308 ID-PCNSL cases, diagnosed at 23 participating sites in 7 countries. Preexisting immunodeficiency included administration of immunosuppressants for transplantation (41.2%) or autoimmunity (36.7%) and HIV infection (21.7%). All  tumors were diffuse large B-cell lymphomas, with EBV detected in  79.2%. Immune reconstitution together with rituximab and methotrexate–based  chemotherapy was associated with the highest response rates and prolonged PFS, irrespective of immunodeficiency subtype and EBV status.  Survival outcomes were highly variable, with a 54-month median overall survival (OS). Multivariable Cox regression identified age (per year increment; hazard ratio [HR], 1.05 (95%  confidence interval [CI], 1.02-1.07); P<0.001), KPS <70 (HR, 3.10; 95% CI, 1.67-5.87; P<0.001), and EBV positivity (HR, 3.26; 95% CI, 1.47-7.33;  P=0.004) as prognostic factors for OS. A prognostic score (IPCG) was developed based on the sum of these  adverse variables (age >60 years, KPS <70, EBV positivity). Stratification by this score yielded median survival times of 135, 29, and 3 months in patients with up to 1, 2, and 3 unfavorable markers (P<0.0001).

It allowed improved prognostic stratification of ID-PCNSL as compared with the Memorial Sloan Kettering Cancer Center and International Extranodal Lymphoma Study Group models developed for immunocompetent PCNSL. Collectively, this large international cohort defines clinicobiological features of ID-PCNSL and introduces a prognostic system with potential to guide future management.