Ghada Elgohary

Leukemia during pregnancy: long term follow up of 32 cases from a single institution.

BACKGROUND AND OBJECTIVES There is limited information regarding the outcome of patients treated for leukemia during pregnancy. This study was performed on all cases of leukemia during pregnancy identified in our institution leukemia database. PATIENTS AND METHODS It is a retrospective study from our existing database. Thirty two cases were identified among the cohort of patients treated for acute and chronic leukemia between January 1991 and July 2003. RESULTS Among the acute leukemia patients (n=21), 10 patients (47.6%) received chemotherapy during pregnancy, seven had live birth and three had spontaneous abortion. No teratogenicity or congenital malformations or postnatal complication were reported. The remaining 11 (52.4%) were not given chemotherapy while pregnant; three patients presented after 34 weeks of gestation ending in normal live births and then received chemotherapy and eight patients had abortion before starting chemotherapy. Among the chronic myeloid leukemia (CML) patients (n=11), nine patients received hydroxyurea, one patient received alfa-interferon and one patient was treated with leukapheresis. Eight patients had normal live births and three patients had abortion. Out of the 32 patients, 18 patients (56.2%) subsequently underwent HLA matched sibling allogeneic stem cell transplantation, seven for acute myeloid leukemia (AML), two for acute lymphocytic leukemia (ALL) and nine for CML. After a median follow up of 16 years, five patients (15.6%) are alive in remission (one from chemotherapy group and four from SCT group). CONCLUSIONS Our report lends credence to the safety and feasibility of administering anti-leukemic therapy in acute and chronic leukemias during pregnancy although acute leukemia patients had possibly a poor long term outcome compared to non-pregnant patients.

Myeloid sarcoma of the vulva post-bone marrow transplant presenting as isolated extramedullary relapse in a patient with acute myeloid leukemia

Myeloid sarcoma is a tumor of myoblasts or immature myeloid cells occurring in an extramedullary site. Myeloid sarcoma of the female genital tract as an isolated initial presentation or isolated relapse is very rare as evidenced from a literature review. We report a case of vulvar myeloid sarcoma presenting as isolated relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT). A 41-year-old female diagnosed with AML M5 achieved remission with chemotherapy and underwent allogeneic HSCT from an HLA-matched sibling donor. The post-transplant period was complicated with chronic graft-versus-host disease. At 10 months post-transplant, she presented with a vulvar mass of six weeks duration. Excisional biopsy of the vulvar mass confirmed the diagnosis of myeloid sarcoma as extramedullary relapse. Bone marrow biopsy was without evidence of leukemia. Involvement of the vulva, vaginal and adjacent cervical area only was confirmed. She received re-induction chemotherapy with clinical regression of both the vulvar, vaginal and the cervical masses; this was followed by radiation therapy to an extramedullary site. The correct diagnosis of myeloid sarcoma, particularly of an isolated mass in the genital area, is important because of its rarity and the need for appropriate institution of therapy.

Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD) over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX) for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2 seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR) in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR) in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

Donor-derived extramedullary acute promyelocytic leukemia post kidney transplant.

Dear Editor, Here, we describe what to our knowledge is the only case in the literature of donor kidney-derived extramedullary acute promyelocytic (EM-APL). A 54-year-old physician with diabetes mellitus, hypertension, and ischemic heart disease, who had received a renal transplant of indeterminate origin for end stage kidney disease in China 2 years before presentation, was referred to our hospital with gross hematuria, deteriorating renal function, jaundice, and multiple subcutaneous nodules. PET CT scan of the body revealed multiple FDG avid masses as shown in Fig. 1a. Biopsy of the transplanted kidney and subcutaneous nodule (FNA) was consistent with granulocytic sarcoma based on flow performed on the submitted specimen (axillary mass) showing a population of cells in the blast gate that co-express MPO, CD11b, CD13, CD33, CD34, CD38, and CD117 and HLA-DR (dim). Bone marrow was uninvolved and a FISH panel including t(15;17) was negative. Attempted cytogenetic analysis from FNA of the nodules failed. A resection of the kidney was offered but the patient declined, and immunosuppression was continued with lowdose FK506 and prednisone; MMF was stopped. The final diagnosis at that stage was granulocytic sarcoma. Given the comorbidities, he was given upfront idarubicin and cytarabine “2+5” with a suboptimal response based on PET scan; then, he received salvage fludarabine/Ara-c (FA) protocol resulted in complete metabolic response. As per standard operating procedure at our hospital, PML-RARa is not sent from a diagnostic tissue sample other than bone marrow. In order to characterize the disease further, a FISH panel on the axillary biopsy was done and revealed positivity for t(15;17). The patient was then given ATRA/idarubicin (AIDA) induction followed by 25 doses of arsenic trioxide (ATO) consolidation and then maintenance ATRA; mercaptopurine and methotrexate were not given due to cytopenias. As the initial lesion seemed to be in the transplanted kidney, we sought to determine whether the leukemia may have been of donor origin. In order to address this hypothesis, DNA was extracted from the previously excised axillary block. This was compared with DNA from the patient’s blood. To our surprise, DNA by short tandem repeat analysis revealed that axillary mass was not of recipient origin as shown (Fig. 1b). Eighteen months on since first presentation, he has no demonstrable disease based on PET scan with good quality of life and stable renal function. A case reported in Blood by Girsberger et al. described a case of donor kidney derived AML [1]. Kidney transplant recipients are at increased risk for development of malignancy compared with the general population [2]. There are case reports of AML post solid organ transplantation [3, 4]. Donor-derived APL has been reported [5]; however, the aleukemic extramedullary presentation in our case is unique. Treatment of acute leukemia in solid organ transplant remains one of the main challenges facing the hematologist with sparse literature focusing on this issue. A. Alhuraiji (*) :W. Chebbo :G. El-Gohary :N. Chaudhri : F. Almohareb :K. Ibrahim : S. A. Osman Hematology Section, Oncology Centre, KFSHRC, Riyadh 11211, Saudi Arabia e-mail: aalhuraiji@gmail.com

Secondary HLH Case Report Highlighting Clinical Challenges

A 19-year-old patient with relapsed acute myeloid leukemia (AML) developed severe and prolonged cytopenia and unexplained jaundice and fever after salvage chemotherapy. His workup revealed hemophagocytosis on the bone marrow biopsy. He was treated for HLH (hemophagocytic lymphohistiocytosis) secondary to AML and chemotherapy. The patient died on day 56 after starting his salvage chemotherapy. Unexpectedly, after his death, the microbiology laboratory reported positive mycobacterial growth from a bronchoalveolar lavage (BAL) sample taken during the workup of his fever. This case illustrates the difficulties in the diagnostic workup of HLH to identify triggers in a timely manner so that a targeted and specific therapy can be administered quickly, given the rapid and deadly evolution of the HLH process.

Extramedullary relapses after allogeneic stem cell transplantation for acute myeloid leukemia: clinical characteristics, incidence, risk factors and outcomes

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplant (allo-HCT) is challenging. Data on extramedullary relapse (EMR) after allo-HCT are limited. We analyzed 215 patients with AML who underwent allo-HCT in our institution between January 2005 and December 2015. We limited this retrospective review to patients who received a MA conditioning, were in complete remission (CR) at the time of transplant and who received a matched sibling transplant, all other patients were excluded to avoid heterogeneity. Seventy-seven (35.8%) patients experienced disease relapse, 45 had BMR, and 32 had EMR. The only variable that was statistically associated with EMR post allo-HCT was male sex (OR = 3.2 (1.2, 8.2), p-value = 0.01); there was a trend for association between transplant in >CR2 and EMR (OR = 0.38 (0.14, 1.06), p-value = 0.06). The median overall survival (OS) after relapse for all relapses was 10 months (95% CI 4.839–15.161). The median OS for BMR group was 8 months (95% CI 2.850–13.150) and 14 months for the EMR group (95% CI 5.776–22.224); however, this was not statistically significant, p-value = 0.4. Multivariate analysis revealed that gender, treatment modality, and time from allo-HCT to relapse (≥12 vs. <12 months) have significant association with the post-relapse death. Male gender was the only significant factor associated with EMR.

CXCR4 (CD184) expression on stem cell harvest and CD34+ cells post-transplant

OBJECTIVES/BACKGROUND CXCR4 is a receptor for stromal-derived factor-1 (SDF-1), a molecule that has a chemotactic activity for lymphocytes and is important in homing of hematopoietic stem cells to their adult marrow. We evaluated the CXCR4 (CD184) expression in the harvest cells and in the post-transplant bone marrow (BM) and its relation to engraftment, as determined by the consensus criteria and chimerism. METHODS This is a prospective study which included 30 patients undergoing hematopoietic stem cell transplantation; 15 patients received autograft and 15 patients received allograft on dates between January 2012 and May 2014. We assessed CD184 (CXCR4) using flow cytometry in the harvest cells together with post-transplant BM assessment on Day 28 and Day 90 for complete morphologic, molecular studies, and detection of CD184 expression on CD34+ cells with chimerism studies on total peripheral blood mononuclear cells. RESULTS Diagnoses of the enrolled patients were as follows: seven (24.1%) with acute myeloid leukemia, eight (27.6%) with multiple myeloma, four (13.8%) with acute lymphoblastic leukemia, three (10.3%) with non-Hodgkin lymphoma, two (6.9%) with myelodysplastic syndromes, two (6.9%) with aplastic anemia, two (6.9%) with chronic myeloid leukemia, one (3.4%) with Hodgkin lymphoma, and one (3.4%) with plasmacytomas. One patient died and was excluded from the study because there were not enough data about engraftment. There was no statistical significance between the level of CD184 in stem cell harvest and the prediction of successful engraftment (p>0.05) as well as in Day 28 BM sample (p>0.05), whereas there was a statistical significance between the level of CD184 in Day 90 BM sample and the occurrence of successful engraftment (p=0.002). CONCLUSION SDF-1/CXCR4 axis plays a crucial role in engraftment; however, more studies are warranted to assess their expression post-transplant. Evaluating the ligand (chemokine, SDF-1) or its receptor (CXCR4) may serve as potential surrogate markers for assessment of engraftment.

Immunoglobulin heavy-chain gene rearrangement in B-cell non-Hodgkin lymphoma using the fluorescence in-situ hybridization technique

Objectives Non-Hodgkin lymphoma (NHL) comprises an extremely heterogeneous group of clonal lymphoproliferative disorders that might be derived from either B-cell or T/NK-cell lineages. The molecular pathogenesis of NHL represents a complex process involving the accumulation of multiple genetic lesions, which include the activation of proto-oncogens such as BCL-1, BCL2, BCL6, and c-MYC by chromosomal translocation, as well as inactivation of tumor-suppressor genes such as TP53 by chromosomal deletion or mutation. Aim of the study The present study aimed to detect immunoglobulin heavy-chain (IgH) gene rearrangement by the fluorescent in-situ hybridization (FISH) technique in paraffin-embedded bone marrow trephine and lymph node biopsies, and to correlate the presence of IgH chain gene rearrangement to the standard prognostic factors of NHL. Participants and methods The present study was carried out on 50 newly diagnosed adults with NHL. The study included 26 diffuse large B-cell lymphoma patients, 21 follicular lymphoma (FL) patients, and three mantle cell lymphoma patients. FISH was performed using LSI 14q break-apart rearrangement probes. Results The IgH gene rearrangement was detected by the FISH technique in lymph node sections of 36 out of 50 patients (72%) and only in six patients (12%) by trephine biopsy; also, it was found that 14q+ve patients were significantly associated with advanced stage of disease as well as low hemoglobin level, high total leukocytic count, low platelet count, high peripheral blood lymphocyte percentage, high lactate dehydrogenase level, and a high International Prognostic Index score. For diffuse large B-cell lymphoma, IgH gene rearrangement was detected in lymph node sections of 17/26 (65.4%) patients and in two patients by trephine biopsy, indicating a highly significant difference. In FL patients, IgH gene rearrangement was detected by the FISH technique in lymph node sections in 16/21 (76%) patients and in one patient (5%) by trephine biopsy, with a high statistical significance. For mantle cell lymphoma, IgH gene rearrangement was detected in all patients 3/3 (100%) both by lymph node and by trephine biopsies. Conclusion This study shows the increasing importance of detailed cytogenetic analysis of NHL cases and focuses on the necessity of use of the FISH technique on lymph node as it identifies early cytogenetic aberrations that are not detected in a bone marrow trephine biopsy, except in stage IV lymphoma.

Eight-hour versus 24-h whole-blood hold before preparation of platelet concentrates by the platelet-rich plasma method

Background Platelet concentrates (PCs) can be prepared by immediate processing of fresh whole blood (WB); alternatively, they can be prepared from WB stored overnight at room temperature. For blood centers, extension of WB storage time from 8 to 24 h would very useful because of significant operational and logistical benefits. This work was carried out to assess the quality of PCs prepared from WB that had been held overnight at ambient temperature compared with that of PCs prepared from fresh WB donations over a 5-day storage period. Study design and methods Thirty units of WB were collected; 15 U were kept at room temperature for 6-8 h before platelet preparation (fresh group) and 15 U were kept in a controlled environment of 20-24°C for 22-24 h before platelet preparation (overnight group). Results PCs prepared after an 8-h or a 24-h hold were comparable in platelet count per PC. CD62P expression and pH values were significantly lower in PCs prepared from 24-h hold donations. Conclusion The quality of PC may in fact improve because of the ambient overnight hold period as evidenced by lower CD62P expression throughout the storage period, which indicates a lower level of platelet activation. The lower pH values detected in overnight PCs remained within the international acceptable range. Egyptian J Haematol 39:-0

Clinical and laboratory presentations of Janus Kinase II-positive patients in Saudi population

Introduction: Janus Kinase II (JAK-II) mutation has a pivotal role in the pathogenesis of the myeloproliferative neoplasms (MPN) and has been shown to be involved in thrombotic complications of these diseases. However, there are limited data regarding clinic-biological features and cytogenetic abnormalities in the Saudi population. Aim: The main aim of this study was to examine clinical presentations, laboratory findings and prognosis of JAK-II-positive Saudi population referred to KFSHRC for testing for variable indications. Methods: A total of 200 patients was referred to our institute for JAK-II mutation testing by polymerase chain reaction based on clinical/laboratory suspicion; about 102 (51%) proved positive. Of the positive cohort, only 62 patients had completed evaluable medical records. Results: Their mean age was 48.2 (range: 16-81) years and 51.6% were males. About 75% had symptoms such as headache 13 [21%]; pruritus 9 [14.5%], visual 7 [11.3%], erythromelalgia 2 [3.2%], and none specific symptoms like fatigue/weakness abdominal discomfort in 30 (48.2%) while the remaining 25% were diagnosed incidentally from abnormal complete blood cells. Clinic-radiological features included: Splenomegaly (53.6%), hepatomegaly (24%), and skin lesions (8%). Thrombosis of portal, hepatic, splenic and mesenteric veins was seen in 24%, stroke and transient ischemic attack in 14%, deep vein thrombosis and pulmonary embolism in 11.2%, ischemic heart disease in 9.6% and 3.2% had arterial thrombosis. The mean peripheral blood count showed white blood cell 13.3 × 109/l, hemoglobin 147.3 g/l and platelets 714 × 109/l. Of the 35 patients evaluated by bone marrow biopsy, the majority (80%) had hyperculluarity. Cytogenetic abnormalities were found in 7 (20%) of the 35 patients and one patient had both JAK-II and BCR/ABL mutations. All the positive patients except 3 (4.8%) were diagnosed as MPNs, 29 (46.7%) polycythemia vera, 24 (38.7%) essential thrombocythemia, 2 (3.2%) primary myelofibrosis and MPN-not otherwise specified in 1 (1.6%). Treatment modalities including hydroxyurea, anagrelide, and thalidomide were used in 75%, antiplatelets were used in nearly 2/3 (61.3%) and 29% of patients required anticoagulants. Three-year actuarial survival was 87% with death related mainly to progressive fibrosis and cytopenia, thrombotic complications necessitating major surgeries, pneumonia or sepsis.