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The 90-day BCR-ABL1 (breakpoint cluster region-Abelson 1) level has been one of the accepted milestones for predicting the molecular response in patients with chronic myeloid leukemia (CML). The rate of decline in BCR-ABL1 has been considered a better predictor of the response but has not been uniformly accepted. A paucity of evidence is available to predict the accuracy of the rate of decline in the Indian context. Therefore, we tested the accuracy of the rate of decline of BCR-ABL1 in predicting the molecular response compared with the single 90-day values in a retrospective cohort study of selected cancer centers in south India.Patients with chronic-phase CML diagnosed from January 2013 to December 2018, the serial BCR-ABL1 levels were estimated at 0, 45, and 90 days, 6 months, and 1 year. Data on patient demographics, risk stratification assessed using the Sokal and EUTOS (European Treatment and Outcome Study) scores were extracted using a mobile-based data capture tool from the medical records of the enrolled patients. The halving time, determined by log reduction, was compared with the 90-day BCR-ABL1 values using the receiver operating characteristic curve for the major and complete molecular response at 6 months and 1 year as standards. Accuracy was determined from the area under the curve. The cutoff for the halving time was chosen to balance the sensitivity and specificity.The rate of decline had more predictive accuracy compared with the 90-day BCR-ABL1 values (area under the curve for rate of decline, 0.83; 90-day, 0.80). A halving time of 20 days identified 95% of the patients who had achieved major molecular response at 12 months compared with 80% using the single 90-day BCR-ABL1 response.The halving time of BCR-ABL1 appears promising as a predictor of the outcomes for patients with CML.

Four patients who presented with autoimmune cytopenias as the sole manifestation of undiagnosed tuberculosis are described here. These were refractory to conventional immunosuppressive therapy and responded dramatically to treatment of the infection. The potential association between tuberculosis and immune hematological conditions is highlighted. Literature is reviewed with respect to possible pathogenetic mechanisms. Clinicians need to be aware of this type of unusual presentation of tuberculosis and must consider this chronic bacterial infection as a potential cause for refractory cytopenias.

PURPOSE Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with Hodgkin lymphoma (HL) relative to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. However, the associated higher cost and toxicity discourage clinicians from prescribing it. Identifying high-risk patients and administering escalated BEACOPP remains an effective strategy. We assessed the significance of interim positron emission tomography (iPET) scan after 2 cycles (iPET2) in identifying this high-risk subset. PATIENTS AND METHODS This cohort study used secondary data from 12 tertiary care centers in South India gathered over 10 years (2008-2018). OS, event-free survival (EFS), determinants of EFS, and complete response (CR) in iPET2 were assessed. RESULTS The study included 409 patients with HL (mean age, 34.5 years; male/female ratio, 1.4:1). The median duration of follow-up was 2.8 years. Of 409 patients, 63% underwent PET-based staging and 37% underwent computerized tomography (CT) staging. Stage IV (28.9%) and bone involvement (9.2%) were seen more often with PET than with CT staging (9.2% and 2%, respectively). Among 171 patients with iPET2 results, 24% did not achieve CR, and no factors were significantly associated. The 5-year EFS and OS rates of the entire cohort were 78% and 97%, respectively. The 5-year EFS and OS rates of patients with CR on iPET2 were 90% and 99%, respectively, whereas these were 65% and 100%, respectively, for patients not achieving CR. On univariable analysis, sex, stage, and iPET2 response significantly predicted inferior EFS. On multivariate analysis, only iPET2 response significantly predicted EFS ( P < .000). CONCLUSION Our study supports the use of PET for staging and iPET2 for response assessment. Nonachievement of CR on iPET2 indicates unfavorable outcome, and such patients may benefit from more intensive treatment.

Isolated mediastinal adenopathy is a diagnostic challenge in the paediatric population, often requiring invasive surgical procedures for diagnosis. We describe a novel minimally invasive modality in a 20 month toddler-transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA). This is the youngest reported use of this modality, highlighting feasibility, technical issues, safety, and rapid diagnosis leading to expedited treatment.

Viral haemorrhagic cystitis (HC) is a significant complication after haematopoietic stem cell transplantation (HSCT), with a potential for major morbidity. The aim of this 7-year analysis of 1160 HSCT patients was to evaluate risk factors for the incidence, severity, toxicity of therapy, clinical course, and outcome of this condition. The overall incidence of HC was 5·8%, with most cases occurring after allogeneic HSCT. Unrelated donors (P = 0·001), non-peripheral blood stem cell source (P = 0·005), myeloablative conditioning (P0·001), use of alemtuzumab in conditioning (P = 0·001), and severe acute graft versus host disease (P0·001) were independent risk factors for an increased incidence of HC post-allogeneic transplant on multivariate analysis. Severe forms of HC were associated with grades II-IV acute graft versus host disease and a longer duration of haematuria. Contrary to previous studies which were carried out on smaller patient populations, busulphan, cyclophosphamide, anti-thymocyte globulin, and total body irradiation were not found to independently increase the risk of viral HC, unless used in a myeloablative combination. Neither duration of viriuria nor peak viral load in urine influenced the severity of HC on multivariate analysis. Severe HC contributed to the deaths of two patients. Overall survival was not statistically different between patient subgroups with non-severe and severe HC.

Outlining the treatment for an unclassifiable lymphoid malignancy is often difficult. A highly undifferentiated lymphomatous mass that relapsed in spite of intense chemotherapy and autologous transplant is reported. At relapse, there was differentiation into myeloid lineage. Though remission was achieved with AML-type reinduction chemotherapy, the mass recurred post allogenic cord blood stem cell transplant.

Clinical bottomline Negative urine antigen test rules out pneumococcal infection with almost 100% certainty (Grade A) A positive test has no practical significance as it can be due to causes other than true infection (Grade B)

In patients heavily pretreated with myelosuppressive chemotherapy or irradiation, Granulocyte colony stimulating factor (G-CSF) may fail to mobilize stem cells from the bone marrow. Plerixafor is emerging as a reliable alternate option in such situations in adult patients. Robust data in support of the high efficacy and safety of plerixafor are available in adults. Very little evidence is available on the usefulness of this drug among children. We report our experience with plerixafor usage on 5 occasions in pediatric patients, with a success rate of 60%. No significant side effects were encountered in any patient.

Life-threatening toxicity is often a contraindication for cytotoxic treatment. Many childhood malignancies have good outcomes with appropriate aggressive chemotherapy. It is not easy to decide whether to subject a child with a good prognostic tumor to a drug that has previously caused significant toxicity. One such situation is documented in this report.

Patients with childhood relapsed and refractory mature B-cell non-Hodgkin lymphoma (B-NHL) and acute lymphoblastic leukemia (B-ALL) are rare and have a dismal prognosis. The previous UK national analysis of 26 children over a 7-year period prior to 1996 had highlighted the poor outcome, with only three survivors. This 10-year multicenter study evaluated recent data, since 2000. Of 33 children, nine survived (27.3%), with a median follow-up of 4.3 years. On exclusion of six children treated with palliative intent, the survival was one-third (nine of 27; 33.3%). All patients with primary refractory disease (n = 7) and all except one with early relapse (n = 11) died. Administration of four doses of 375 mg/m(2) of rituximab was associated with a longer survival (p = 0.006). Response to reinduction (p < 0.001) and autologous hematopoietic stem cell transplant (auto-HSCT) (p = 0.003) were significant on multivariate analysis. Patients with a time to relapse of at least 6 months are potentially curable and must be offered intensive treatment with salvage chemotherapy, rituximab and auto-HSCT.

Diseases of blood and lymphoreticular system can have multisystem manifestations. Rheumatologic involvement has been reported in association with many benign and malignant haematological disorders; these patients are equally likely to present to both clinical rheumatologists and haematologists. This review focuses on the well-described rheumatologic features, other occasionally reported rheumatologic manifestations and unusual musculoskeletal complications related to the treatment in patients with underlying haematological conditions. The aim of this review is to help increase the awareness of rheumatologic manifestations seen in the blood disorders and to highlight the potential diagnostic pitfalls.

Sporopachydermia cereana is a cactophilic yeast, which is not recognised as a human pathogen. We describe two fatal infections with this fungus in profoundly neutropenic patients. S. cereana escapes detection by conventional mycological identification methods. This organism may be an under-recognised cause of fatal fungal sepsis among immunocompromised patients.

Hematological cancers and non-malignant hematological disorders are biologically diverse conditions and are treated differently. We compared the pattern of EBV infections following allogeneic stem cell transplantation between the above two groups of hematological disorders. Eighty-three transplants were evaluated over a consecutive 7-year period at a single center. No difference was found in the incidence of post-transplant EBV infections between the two groups, though a higher median peak viral load was noted in the non-malignant group (P=0·04). Pre-transplant immunosuppressive therapy with antithymocyte globulin (ATG) significantly increased the risk of post-transplant EBV infections (P=0·04) in the non-malignant group patients. No significance was found for prior cytotoxic chemotherapy among the malignant group of patients. Alemtuzumab based conditioning was not associated with an increased risk for EBV infections in either of the groups. Treatment with two or more courses of ATG was found to be significantly associated with post-transplant EBV-related PTLD (P=0·01). Post-transplant EBV infections did not influence overall survival (non-malignant, P=0·66; malignant, P=0·41) in either of the subgroups. There were no deaths directly attributable to EBV infections.

The haematological indications for allogeneic stem cell transplantation can be broadly divided into non-malignant and malignant disorders. We compared the incidence and risk factors for post-transplant cytomegalovirus (CMV) infections between these two biologically diverse subgroups of haematological conditions. Out of 105 allogeneic transplants, 64 and 41 were for underlying non-malignant and malignant indications respectively. CMV infections were significantly more frequent (P=0.016) in the malignant subgroup. Pre-transplant recipient CMV seropositivity in both subgroups (negative versus positive; non-malignant,P=0.023; malignant, p0.001), donor seropositivity (P=0.002) and acute graft-versus-host disease (GVHD) (P=0.02) in the non-malignant subgroup andor =3 courses of previous cytotoxic therapy (P=0.023) in the malignant subgroup were found to be associated with an increased risk of CMV infections. On multivariate analysis, donor seropositivity in the non-malignant patients (negative versus positive,P=0.022; odds ratio: 0.18) and recipient seropositivity in patients with malignancies (negative versus positive; P=0.001, odds ratio: 0.01) were identified to be significant factors for risk of CMV infection.

To the Editor, Unlike with acute forms of leukaemia, fungal infections are rare in chronic lymphocytic leukaemia (CLL). Most previous reports have been on patients with prolonged neutropenia or after allogeneic stem cell transplantation (SCT). We would like to document a patient with CLL who had a fungal infection at unusual sites as a result of combination therapy with alemtuzumab (Campath-1H) and methyl prednisolone. This patient was neither neutropenic nor had he received SCT. A 65-year-old man was on treatment with alemtuzumab, methyl prednisolone and ciclosporin for relapsed CLL and autoimmune haemolytic anaemia. He had a neutrophil count of 2.7 9 10/L with normal serum levels of immunoglobulins and was hence not on prophylactic antimicrobials. He presented with acute onset of pain in his right eye and developed a partial loss of vision in his right temporal field over the next 24 h in the absence of fever or raised inflammatory markers. He was referred to a tertiary care centre for ophthalmological evaluation and management. Examination of the right eye revealed pan-uveitis with a vitreous abscess (Fig. 1). A vitreous biopsy showed infection by Aspergillus fumigatus. MRI scan of the brain revealed a 4 mm ring-enhancing lesion in the cortex of the left frontal lobe, consistent with cerebral aspergillosis (Fig. 2). Toxoplasma serology was negative. A highresolution CT scan of his chest was normal. He was treated with oral voriconazole and intravitreal amphotericin instillations complicated by vitreal haemorrhage due to thrombocytopenia. Both the fungal infection and the haemorrhage improved over the next 6 weeks and his vision cleared gradually. A repeat MRI scan of his brain showed complete resolution of the lesion. The combination of alemtuzumab and high-dose methyl prednisolone (CamPred) is now increasingly being used to treat patients with CLL refractory to purine analogues and those with deletions of the TP53 gene [1–3]. Alemtuzumab, a humanised anti-CD52 monoclonal antibody, targets both B and T lymphocytes in addition to monocytes, macrophages and a subset of antigen-presenting dendritic cells. It thus significantly impairs the immunological surveillance mechanisms against infections. Whilst on this heavily immunosuppressive regimen, a high index of suspicion against viral reactivations and fungal

The precise effects of CD34+ cell dose on the outcome of allogeneic transplantation for aplastic anaemia (AA) are not known. Previous studies have used the total mononuclear cell count to quantify stem cell dose. We evaluated the effects of CD34+ cell dose on the clinical and haematological end points of transplantation. The transplant variables and outcome parameters on 46 patients with acquired AA were assessed by comparing low vs high CD34+ cell doses. Infusion of less than 2 x 10(6)/kg of CD34+ cells was associated with an increased incidence of graft failures (P=0.03), higher incidence of bacterial infections (P=0.006) and a delay in the engraftment of neutrophils (P=0.046). The latter was found to be an effect of stem cell source (non-PBSC) rather than the CD34+ count. Other parameters, such as plt engraftment (P=0.63), red cell (P=0.94) and plt (P=0.31) transfusion independence, chimerism, acute and chronic GVHD (P=1.0) and OS (P=0.57), were not significantly influenced by the CD34+ cell dose. These findings are different to the published studies on the relevance of CD34+ cell dose in allogeneic transplantation for haematological cancers.

The presence of 2 active primary tumors in a child is both unusual and challenging. This places the clinician and the family in a difficult situation while planning the treatment. The concurrent presence of a low-grade brain stem glioma and acute lymphoblastic leukemia in a genetically normal girl is presented. The problems encountered with diagnosis and treatment are discussed here.

About a quarter of children with Down syndrome and transient abnormal myelopoiesis (TAM) progress to acute megakaryoblastic leukemia (AMKL). We describe isolated dysmegakaryopoiesis despite complete resolution of TAM in an 18-month-old girl, who developed AMKL 6 months later.

Hematologists are frequently involved with morphological analysis of centrifuged cerebrospinal fluid (CSF) for the diagnosis of malignant infiltration of the central nervous system (CNS). Although malignant cells in the CSF are most often due to underlying hematological cancers, leptomeningeal carcinomatous infiltration from a solid tumor is not uncommon. A 46-year-old lady presented with focal neurological signs suggestive of cauda equina compression. She was on adjuvant therapy for invasive ductal carcinoma of breast with expression of human epidermal growth factor receptor2 (HER-2). MRI scan confirmed a metastatic deposit in the conus medullaris with tumor nodules in the cauda equina and diffuse meningeal enhancement. Clear CSF was obtained from a diagnostic lumbar puncture and microscopy showed the presence of 50/mm white cells and 10/ mm red cells, with no evidence of infection. A centrifuged cytospin preparation of CSF stained with May-GrunwaldGiemsa (MGG) showed numerous small lymphocytes, neutrophils, metamyelocytes, and metastatic breast carcinoma cells (Image 1). The latter cells were much larger than the hematological cells, with homogeneous nuclei containing open chromatin and abundant cytoplasm with prominent blebs from the cell surface (Image 1). HER-2 positive breast cancers are known to carry a higher risk for CNS metastasis [1]. The presence of lymphocytosis and granulocytosis in this nonhemorrhagic CSF is a likely localized inflammatory response to metastasis from the breast carcinoma.