Naeem Chaudhri

Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation

Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources (e.g. umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, periand post-transplant exposures and risk-factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplant experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This review provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.

Ocular Findings after Allogeneic Hematopoietic Stem Cell Transplantation

OBJECTIVE To study the incidence, causes, and outcome of major ocular complications in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). DESIGN Retrospective, noncomparative, observational clinical study. PARTICIPANTS The study included a total of 620 patients who underwent allogeneic HSCT in the period from 1997 to 2007 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. INTERVENTION Allogeneic HSCT. MAIN OUTCOME MEASURES Patients with ocular complications were referred to the ophthalmology division for complete ophthalmologic examination, including visual acuity, tonometry, Schirmer test, biomicroscopy, and dilated ophthalmoscopy. Laboratory investigations were performed whenever indicated. The incidence and causes of major ocular complications after allogeneic HSCT were determined. Visual acuity at 1 year after allogeneic HSCT was recorded. RESULTS Major ocular complications occurred in 80 (13%) of 620 patients who underwent allogeneic HSCT. There were 36 male patients (45%) and 44 female patients (55%) with a mean age of 29 years and an age range of 9 to 65 years. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate in 69 patients, and cyclosporine, methotrexate and corticosteroids, or mycophenolate mofetil in 11 patients. The most frequently encountered ocular complications were chronic GVHD, dry eye syndrome without GVHD, corneal ulcers, cataract, glaucoma, cytomegalovirus retinitis, fungal endophthalmitis, and acquisition of allergic conjunctivitis from atopic donors. There was no correlation between the pattern of ocular complications and the transplanted stem cell source. Best-corrected visual acuity (BCVA) at 1 year after transplantation was less than 20/200 in 13 patients (16%), less than 20/50 in 17 patients (21%), and better than 20/50 in 50 patients (63%). CONCLUSIONS Ocular complications are common in patients undergoing allogeneic HSCT. Early recognition and prompt treatment are important. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Special issues related to hematopoietic SCT in the Eastern Mediterranean region and the first regional activity report

Although several centers are now performing allogeneic hematopoietic SCT (HSCT) in the Eastern Mediterranean (EM) region, the availability is still limited. Special issues including compatible donor availability and potential for alternative donor programs are discussed. In comparison to Europe and North America, differences in patterns of diseases and pre-HSCT general status, particularly for patients with BM failure, are described. Other differences including high sero-positivity for CMV, hepatitis B and C infection, and specific observations about GVHD and its relation to genetically homogeneous communities are also discussed. We report that a total of 17 HSCT programs (performing five or more HSCTs annually) exist in 9 countries of the EM region. Only six programs are currently reporting to European Group for Blood and Marrow Transplantation or Center for International Blood and Marrow Transplantation Research. A total of 7617 HSCTs have been performed by these programs including 5701 allogeneic HSCTs. The area has low-HSCT team density (1.56 teams per 10 million inhabitants vs 14.43 in Europe) and very low-HSCT team distribution (0.27 teams per 10 000 sq km area vs <1–6 teams in Europe). Gross national income per capita had no clear association with low-HSCT activity. Much improvement in infrastructure and formation of an EM regional HSCT registry are needed.

Incidence of thyroid cancer in the Kingdom of Saudi Arabia, 2000–2010

BACKGROUND Thyroid cancer is the second most common malignancy among females at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and in Saudi Arabia, accounting for about 11% of all newly diagnosed female cancers in the country in 2008. Over the past several decades, an increasing incidence of thyroid cancer has been reported in the Kingdom of Saudi Arabia. There are no comprehensive clinical epidemiological data for the trends of thyroid cancer incidence compared to the global incidence. This report reviews the thyroid cancer incidence in KFSH&RC and compares that with Saudi Arabia, the Gulf region, North America and globally from 2000 to 2010. METHODS Retrospective review of patients with thyroid cancer was carried out from 2000 to 2010, using the hospital Tumor Registry program as per the American College of Surgeons standards. Trends and patterns of all well-known prognostic factors were sub-stratified by age, stage and grade. RESULTS A total of 2292 patients with thyroid cancer were treated at KFSH&RC, Riyadh, Saudi Arabia, from 2000 to 2010. Thyroid cancer constitutes about 9% of all malignancies and 12% of all female malignancies at KFSH&RC, which are significantly higher compared to the USA, where thyroid cancer represents only 2.9% of all malignancies and 4.6% of all female malignancies. Papillary adenocarcinoma was the most common histological subtype followed by papillary carcinoma, follicular variant. Median age at diagnosis was 40 for females and 44years for males. Overall Age-Standardized Incidence Rate (ASR) was 4.4/100,000 (6.8 for female and 2/100,000 for males) in the Kingdom in 2008. Median age at diagnosis was 38years and the highest incidence was in the 30-39year age group in KFSH&RC. About 48% of patients presented in the localized stage and 60% underwent combined modality treatment consisting of surgery, radiation and hormonal therapy. There was significantly increased incidence among females as compared to males. The age-adjusted thyroid cancer incidence rates from 2000 to 2010 varied three-fold more for females than for males. Considerable geographical variations were present in thyroid cancer incidence in Saudi Arabia. CONCLUSION Thyroid cancer incidence rates have increased exponentially between 2000 and 2010 and there is significant geographical variation in the incidence of thyroid cancer throughout the Kingdom. Thyroid cancer has become the second most common cancer among young Saudi women with a male to female ratio at 0.3:1. Rising incidence of thyroid cancer in Saudi Arabia may be due to the increased detection and diagnosis of the thyroid cancers and not only an increase in the true occurrence of thyroid cancer. More studies are required to determine this significant difference at the molecular level.

Successful treatment of hepatic veno-occlusive disease after myeloablative allogeneic hematopoietic stem cell transplantation by early administration of a short course of methylprednisolone

Hepatic veno-occlusive disease (VOD) is one of the most common and important regimen-related toxicities observed after hematopoietic stem cell transplantation (HSCT). There are no universally accepted preventative or therapeutic approaches for VOD. We prospectively evaluated the safety and efficacy of a short course of methylprednisolone (MP) in 48 patients undergoing allogeneic HSCT who were diagnosed with hepatic VOD. MP was administered at a dose of 0.5 mg/kg i.v. every 12 h for a total of 14 doses, and then discontinued without taper. Thirty (63%) patients responded with a reduction in total serum bilirubin of 50% or more after 10 days of treatment. In univariate analysis, non-responders had a higher total bilirubin at the start of MP therapy, more weight gain, evidence of fungal infection and platelet refractoriness. High SGPT and early engraftment were significant factors among responders. Twenty-five of the 30 responders survived up to day +100, whereas all but three non-responders died within 100 days post-HSCT, for a probability of survival of 58% among responders and 10% for non-responders. Prospective comparative studies are needed to confirm the observed encouraging outcome of MP therapy for VOD.

Second allogeneic bone marrow transplantation after myeloablative conditioning analysis of 43 cases from single institution.

Abstract Between March 1984 and December 1999, a total of 43 second related allogeneic BMT procedures after myeloablative conditioning were carried out in our institution, 37 following allogeneic, and 6 following autologous BMT. Thirty one patients were males (72%). At 1st BMT (BMT1), median age was 11.5 years (range, 0.16-45 years). BMT1 was carried out for the diagnosis of AML in 13 patients (30%), SAA in nine (21%), ALL in six (14%), CML in six (14%), immunodeficiency in three (7%), NHL in two, β-thal in two, HD in one, Red cell aplasia in one. HLA matching status for allogeneic BMT1 was full match in 33, one antigen mismatch in two and haplo identical in two patients. Median age at the 2nd BMT (BMT2) was 14 years (range, 0.41-46.7 years). Indications for BMT2 were recurrent hematologic neoplasm in 23 patients (53%), primary graft failure in 12 (28%) and late graft failure in 8 (19%). Median time from BMT1 to recurrence of hematologic neoplasm or late graft failure was 10 months (range, 2.5- 88 months). Median BMT1 to BMT2 interval was 13 months (range, 1-107 months). For BMT2, the same donor was used in 29 patients, while 14 patients had alternate related donor (12 full match, 1-one Ag mismatch, 1 haplo identical). A different conditioning regimen was used in the majority of the patients (39, 91%). Radiation containing conditioning regimen were used mostly for patients previously conditioned with chemotherapy only for BMT1 and chemotherapy conditioning±ATG for those who received radiation containing conditioning at BMT1. Bone marrow was the stem cell source for all patients at BMT2 and all except three autologous peripheral stem cell transplantation patient at BMT1. Significant organ toxicity leading to procedure related death in 13 patients (30%) was observed after BMT2. At a median follow up of 36 months after BMT2, 22 patients (51%) are alive (20 free of disease, 2 with recurrent disease) with overall median survival of 47.5 (SD±9) months. Univariate analysis of relevant clinical factors identified the following variables as the only statistically significant favorable prognostic factors for overall survival: BMT1-BMT2 interval of ≥6 months (P=0.0007) and age at BMT2 ≤10 years (P=0.041). The nature of underlying disease (neoplastic or non-neoplastic) was not statistically significant (P=0.23). There was no statistically significant difference in survival outcome of BMT2 using same donor vs. alternate related donor (P=0.51). Due to the relatively limited sample size, multivariate analysis was not attempted. This single institution study suggests that second allogeneic BMT after myeloblative conditioning has an acceptable treatment related morbidity/mortality and favorable outcome if performed at age ≤10 years and with an interval of ≥6 months after the first BMT. Additionally same donor can successfully be used for the second transplant with similar survival outcome to alternate donor.

Fludarabine-Based Conditioning Chemotherapy for Allogeneic Hematopoietic Stem Cell Transplantation in Acquired Severe Aplastic Anemia

Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naïve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m(2)/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 10(8)/kg (range, 0.60-6.7 × 10(8)/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naïve patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner.

Allogeneic Hematopoietic Stem Cell Transplantation in Adolescent and Adult Patients with High-Risk T Cell Acute Lymphoblastic Leukemia

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is often recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (≥CR2) and sometimes in high-risk (HR) patients in first complete remission (CR1). Between January 1995 and July 2009, 53 patients with HR T-ALL underwent allo-SCT at our institution. Median age was 18 years (range, 14-51). Thirty-two patients (60.3%) were in CR1, 18 (34%) were in ≥CR2, and 3 (5.7%) were in relapse. The cumulative incidence of nonrelapse mortality at 5 years was 22.5%. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 40.2%, and that of chronic GVHD was 43.7%. The majority of relapses (88.9%) occurred within 1 year after SCT. The cumulative incidence of relapse (CIR) at 5 years was 35.6%. CIR was 29.8% in patients in CR1, 35.3% in patients in ≥CR2 and all patients transplanted in relapse had disease recurrence post-allo-SCT (P = .000). Overall survival (OS) and disease-free survival (DFS) at 5 years were 43.5% and 41.8%, respectively. The 5-year OS was 53.5% (95% CI 34.5%-72.5%) and 5-year DFS was 52% (95% CI 33%-71%) in patients who underwent allo-SCT in CR1, compared with 31.9% (95% CI, 9%-54.8%) and 29.4% (95% CI 7.6%-51.2%) in those who underwent allo-SCT in ≥CR2. On multivariate analysis, disease status at SCT remained significantly associated with OS (P = .007), DFS (P = .002), and CIR (P = .000). The presence of extramedullary disease at diagnosis had no effect on the different outcomes. Grade II-IV acute GVHD was significantly associated with a lower OS (P = .006) and DFS (P = .01). Our data indicate that allo-SCT represents an effective treatment for HR T-ALL, particularly when performed in CR1.

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.