1.Double Philadelphia chromosome-positive B acute lymphoblastic leukaemia in an elderly patient
Tang Yee-Loong ; Raja Zahratul Azma Raja Sabudin ; Leong Chooi-Fun ; Clarence Ko Ching-Huat
The Malaysian Journal of Pathology 2015;37(3):275-279
A rare case of double Philadelphia chromosome-positive B Acute lymphoblastic Leukaemia (B-ALL)
is reported here. A 60-year-old lady presented with one month history of fever, submandibular
lymphadenopathy, loss of appetite and weight loss. Physical examination revealed multiple palpable
cervical lymph nodes. Blood film showed leucocytosis with 72% blasts. Bone marrow assessment
confirmed a diagnosis of B-ALL with presence of double Philadelphia (Ph) chromosomes. As she was
very ill, she was initially treated with an attenuated regimen of induction chemotherapy consisting
of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) along with intrathecal
chemotherapy comprising methotrexate, cytarabine and hydrocortisone. Bone marrow examination
post-induction chemotherapy showed >5% blasts. She was subsequently re-induced with rituximab,
cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) along with intrathecal
chemotherapy, following which she went into complete remission. Consolidation chemotherapy
consisting of methotrexate, methylprednisolone, cytarabine, intrathecal chemotherapy and imatinib
was subsequently administered followed by maintenance chemotherapy consisting of vincristine,
prednisolone and imatinib (IDEAMOP). She developed spontaneous bruises and relapsed four
months into her maintenance chemotherapy with 90% blasts in the bone marrow which was treated
with fludarabine, cytarabine and granulocyte colony stimulating factor (FLAG). Unfortunately she
developed neutropenic sepsis which was complicated by invasive lung aspergillosis. Bone marrow
examination post-FLAG showed 80% blasts. Despite aggressive antifungal therapy, her lung infection
worsened and she finally succumbed to her illness 13 months after the initial diagnosis. We highlight
a rare case of elderly B-ALL with double Ph chromosomes which carries a poor prognosis despite
aggressive treatment for the disease and its complications.
2.Extensive myelofibrosis responsive to treatment for acute erythroblastic leukaemia.
S-Abdul-Wahid Fadilah ; Raja-Sabudin Raja-Zahratul-Azma ; Chooi-Fun Leong
The Malaysian journal of pathology 2006;28(1):55-8
Intense myelofibrosis is rarely associated with de novo acute myeloid leukaemia (AML) except in acute megakaryoblastic leukaemia (AML-M7) where there is diffuse marrow fibrosis as a consequence of proliferation of neoplastic myeloid cells. AML associated with significant myelofibrosis developing both de novo or secondary to primary (idiopathic) myelofibrosis is characterised by a fulminant course and extremely poor prognosis, primarily due to treatment-resistant disease. The prognostic value of degree of marrow fibrosis in de novo AML has been poorly investigated. We describe a case of extensive myelofibrosis associated with acute erythroblastic leukaemia (AML-M6) that responded to induction therapy of the leukaemia.
Myelofibrosis
;
Acute
;
Leukemia, Myelocytic, Acute
;
therapeutic aspects
;
prognostic
3.Detection of α-thalassaemia in neonates on cord blood and dried blood spot samples by capillary electrophoresis
Hafiza Alauddin ; Mustafa Langa ; Malisa Mohd Yusoff ; Raja Zahratul Azma Raja Sabudin ; Mpath, Azlin Ithnin ; Noor Hamidah Hussin
The Malaysian Journal of Pathology 2017;39(1):17-23
Haemoglobin Bart’s (Hb Bart’s) level is associated with α-thalassaemia traits in neonates,
enabling early diagnosis of α-thalassaemia. The study aimed to detect and quantify the Hb Bart’s
using Cord Blood (CB) and CE Neonat Fast Hb (NF) progammes on fresh and dried blood spot
(DBS) specimen respectively by capillary electrophoresis (CE). Methods: Capillarys Hemoglobin
(E) Kit (for CB) and Capillarys Neonat Hb Kit (for NF) were used to detect and quantify Hb Bart’s
by CE in fresh cord blood and dried blood spot (DBS) specimens respectively. High performance
liquid chromatography (HPLC) using the β-Thal Short Programme was also performed concurrently
with CE analysis. Confirmation was obtained by multiplex ARMS Gap PCR. Results: This study
was performed on 600 neonates. 32/600 (5.3%) samples showed presence of Hb Bart’s peak using
the NF programme while 33/600 (5.5%) were positive with CB programme and HPLC methods.
The range of Hb Bart’s using NF programme and CB programme were (0.5–4.1%) and (0.5-7.1%),
respectively. Molecular analysis confirmed all positive samples possessed α-thalassaemia genetic
mutations, with 23/33 cases being αα/--SEA, four -α3.7/-α3.7, two αα/-α3.7 and three αα/ααCS. Fifty Hb
Bart’s negative samples were randomly tested for α-genotypes, three were also found to be positive
for α-globin gene mutations. Thus, resulting in sensitivity of 91.7% and 88.9% and specificity of
100% for the Capillarys Cord Blood programme and Capillarys Neonat Fast programme respectively.
Conclusion: Both CE programmes using fresh or dried cord blood were useful as a screening tool
for α-thalassaemia in newborns. All methods show the same specificity (100%) with variable, but
acceptable sensitivities in the detection of Hb Bart.
4.Hb Lepore/β0-Thalassaemia With α+-Thalassaemia Interactions, A Potential Diagnostic Pitfall
Hafiza Alauddin ; Suziana Mohamad Nasir ; Madzlifah Ahadon ; Raja Zahratul Azma Raja Sabudin ; Azlin Ithnin ; Noor Hamidah Hussin ; Hamidah Alias ; Loh C-Khai ; Zarina Abdul Latiff ; Nor Azian Abdul Murad ; Ainoon Othman
The Malaysian Journal of Pathology 2015;37(3):287-292
Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a
heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other
haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We
reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly
at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of
both patients showed features of thalassaemia intermedia. Other laboratory investigations of the
patients showed conflicting results. However, laboratory investigation results of the parents had led
to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance
α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly
in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis,
hence appropriate clinical management and genetic counseling.
5.Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall.
Alauddin, Hafiza ; Mohamad Nasir, Suziana ; Ahadon, Madzlifah ; Raja Sabudin, Raja Zahratul Azma ; Ithnin, Azlin ; Hussin, Noor Hamidah ; Alias, Hamidah ; Loh, C-Khai ; Abdul Latiff, Zarina ; Abdul Murad, Nor Azian ; Othman, Ainoon
The Malaysian Journal of Pathology 2015;37(3):287-92
Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.
6.Comparison of Clinicopathological Parameters, and Treatment Responses in Younger and Older Chronic Myeloid Leukaemia Patients Treated with Imatinib
Ahmad Farhan Kamarudin ; Sivakumar Palaniappan ; Raja Zahratul Azma Raja Sabudin ; Salwati Shuib ; Siti Afiqah Muhamad Jamil ; Nor Rafeah Tumian
Malaysian Journal of Medicine and Health Sciences 2023;19(No.6):101-110
Introduction: Differences in baseline characteristics and response to treatment in different age groups of patients with chronic myeloid leukaemia (CML) in resource-limited countries have not been extensively studied. We aimed to determine the differences in clinicopathological parameters at diagnosis and response to imatinib in adult CML patients with younger (under 60 years; YCML) and older (60 years and older; OCML) age treated at our institution from March 2001 to March 2021. Methods: A retrospective analysis of consecutive adult CML patients receiving imatinib was performed. Clinicopathological parameters and treatment response were reviewed and analysed using
hospital medical records and electronic data reports. Results: The median age at diagnosis was 50 years. OCML patients (n=17) had significantly more comorbidities. The YCML group (n=50) generally had a palpable spleen >5cm from the costal margin, mild anaemia, hyperleukocytosis and thrombocytosis. A starting dose of 400 mg/day was observed in 84% of YCML and in 65% of OCML. Cumulative complete cytogenetic response was 50% in YCML versus 70.6% in OCML, p=0.158. OCML tended to have a higher percentage of major molecular response (MMR) (52.9%
versus 32%) and a shorter time to MMR, 22 months (range 5-70) versus 35 months (range 8-53). OCML experienced more haematological and non-haematological treatment-related adverse events after imatinib therapy. Conclusion: Although OCML patients had more comorbidities and treatment intolerances, overall long-term treatment response was comparable to YCML. In OCML, a more personalised approach to initial and subsequent dosing of imatinib may be considered.