|Year : 2018 | Volume
| Issue : 1 | Page : 9-15
Long term clinical outcomes of adult hematolymphoid malignancies treated at Tata Memorial Hospital: An institutional audit
Navin Khattry1, Siddhartha Laskar2, Manju Sengar1, Venkatesh Rangarajan3, Tanuja Shet4, PG Subramanian5, Sridhar Epari4, Bhausaheb Bagal1, Jayant Sastri Goda2, Archi Agarwal3, Hasmukh Jain1, Prashant Tembhare5, Nikhil Patkar5, Nehal Khanna2, Sachin Punatar1, Anant Gokarn1, Dhanlakshmi Shetty6, Hemani Jain6, Avinash Bonda1, Vikram Gota7, Syed Hasan8, Jyoti Kode8, Shilpee Dutt8, Suyash Kulkarni9, Nitin Shetty9, Nilesh Sable9, Jayita Deodhar10, Sunita Jadhav11, Preeti Pawaskar1, libin Mathew1, Hari Menon1, Reena Nair1, Sadhana Kannan12, Shubhadha Chiplunkar8, Sumeet Gujral4
1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, India
4 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
5 Department of Hematopathology, Tata Memorial Centre, Mumbai, Maharashtra, India
6 Department of Cancer Cytogenetics, Tata Memorial Hospital, Mumbai, Maharashtra, India
7 Department of Clinical Pharmacology, Tata Memorial Centre, Mumbai, Maharashtra, India; Homi Bhabha National Institute (HBNI), Training School Complex, Anushakti Nagar, Mumbai, Maharashtra, India
8 Cancer Research Institute, Tata Memorial Centre, Mumbai, Maharashtra, India; Homi Bhabha National Institute (HBNI), Training School Complex, Anushakti Nagar, Mumbai, Maharashtra, India
9 Department of Radiology, Tata Memorial Hospital, Mumbai, Maharashtra, India
10 Department of Psychiatry and Palliative Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, India
11 Social Welfare, Tata Memorial Hospital, Mumbai, Maharashtra, India
12 Department of Biostatistics, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India
|Date of Web Publication||23-Aug-2018|
Dr. Navin Khattry
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: There is paucity of data from India about the outcomes of patients with various hematological malignancies. Since its formation in 2009, the adult hematolymphoid disease management group of the Tata Memorial Centre is dedicated to the treatment of hematological malignancies alone. In this report, we present the outcomes of patients treated at our centre over a 5 year period for various haematological malignancies in both transplant and non-transplant setting. Methods: This is a retrospective analysis of all patients registered in adult hematolymphoid disease management group between 1st January 2010 to 31st December 2014. Patients not treated at our centre were excluded from survival analysis. The cut off date for survival analysis was 31st January 2016. Results: Overall, 1869, 3633 and 544 patients with acute leukemias, various lymphomas and myeloma respectively were registered at our centre from 1st January 2010 to 31st December 2014. Of these, 1178 (63%), 3091 (85%) and 454 (83%) respectively received treatment at our centre. The cumulative probability of 5 year overall survival for patients with acute leukemias, Hodgkin's lymphoma, non-Hodgkin lymphoma and myeloma treated at our centre is 40%, 85%, 78% and 40% respectively. Four hundred and fifteen stem cell transplants were done between 14th November 2007 to 31st December 2014 with 46% being allogeneic and 54% being autologous. The 5 year overall survival of patients with allogenic and autologous transplant was 52% and 63% respectively. Conclusions: This is the largest single centre data on outcomes of various haematological malignancies from India. This real world data identifies areas which need further attention to improve outcomes.
Keywords: Hematological malignancies, hematolymphoid disease management group, outcomes
|How to cite this article:|
Khattry N, Laskar S, Sengar M, Rangarajan V, Shet T, Subramanian P G, Epari S, Bagal B, Goda JS, Agarwal A, Jain H, Tembhare P, Patkar N, Khanna N, Punatar S, Gokarn A, Shetty D, Jain H, Bonda A, Gota V, Hasan S, Kode J, Dutt S, Kulkarni S, Shetty N, Sable N, Deodhar J, Jadhav S, Pawaskar P, Mathew l, Menon H, Nair R, Kannan S, Chiplunkar S, Gujral S. Long term clinical outcomes of adult hematolymphoid malignancies treated at Tata Memorial Hospital: An institutional audit. Indian J Cancer 2018;55:9-15
|How to cite this URL:|
Khattry N, Laskar S, Sengar M, Rangarajan V, Shet T, Subramanian P G, Epari S, Bagal B, Goda JS, Agarwal A, Jain H, Tembhare P, Patkar N, Khanna N, Punatar S, Gokarn A, Shetty D, Jain H, Bonda A, Gota V, Hasan S, Kode J, Dutt S, Kulkarni S, Shetty N, Sable N, Deodhar J, Jadhav S, Pawaskar P, Mathew l, Menon H, Nair R, Kannan S, Chiplunkar S, Gujral S. Long term clinical outcomes of adult hematolymphoid malignancies treated at Tata Memorial Hospital: An institutional audit. Indian J Cancer [serial online] 2018 [cited 2018 Dec 11];55:9-15. Available from: http://www.indianjcancer.com/text.asp?2018/55/1/9/239607
| » Introduction|| |
Tata Memorial hospital is the largest dedicated cancer center in India and Asia. The center has about 50,000 registrations annually since the past few years. With the ever-increasing registrations, in order to improve patient care (and also to improve research and education), disease management groups (DMGs) were formed. Each of these groups is formed by clinicians, radiologists, pathologists, social service staff, and other supportive staff – all involved in the care of patients with a particular group of cancers. The adult hematolymphoid (AHL) group is one of these groups, which started functioning in 2009. The group comprise medical oncologists, radiation oncologists, pathologists, hematopathologists, basic scientists, cytogeneticists, nuclear medicine specialists, and clinical pharmacologists. It caters to patients with leukemias, lymphomas, plasma cell dyscrasias, and other hematological malignancies. There is also a dedicated hematopoietic stem cell transplant unit as a part of this DMG. In this study, we report the activity and outcome data of various hematological malignancies treated at our center from January 1, 2010 to December 31, 2014.
This is a retrospective analysis of all patients registered in adult hematolymphoid disease management group between 1st January 2010 to 31st December 2014. Patients not treated in our centre were excluded from survival analysis. The cut off date for survival analysis was 31st January 2016 for all patients who did not undergo transplant while the cut off date for those who underwent transplant was 31st August 2017. For patients who did not undergo transplant, only overall survival (OS) was reported which was calculated from date of diagnosis to date of death or last follow up (LFU) if alive. For patients who underwent transplant, both OS and relapse free survival (RFS) were reported in which OS was calculated from date of transplant to death or LFU if alive and RFS from date of transplant to date of progression or death or LFU if alive and disease free. Kaplan –Meir method was used for survival analysis.
| » Activity and Outcome Data of Various Hematological Malignancies|| |
Acute leukemia activity and outcome
Between January 1, 2010 and December 31, 2014, 1869 patients of acute leukemia were registered in Tata Memorial Hospital (TMH) [Figure 1]. The median age of the entire cohort was 30 years (range 11–86 years) with 1293 (69%) males, giving a male/female ratio of 2.2:1. Six hundred and ninety-one patients (37%) were excluded from analysis as these patients were advised upfront palliation or were lost to follow-up during the workup phase. Eventually, 1178 patients were treated at TMH. Acute promyelocytic leukemia (APML) comprised 92 patients, while acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) comprised 513 and 560 patients, respectively. The median age of the treated cohort was 29 years with male/female ratio of 2.2:1. In general, patients with AML (other than APML) were treated by the standard 3 + 7 induction chemotherapy followed by high-dose cytarabine (HiDAC) as consolidation chemotherapy. Our policy is to give 3 cycles of HiDAC as routine. Patients in intermediate and high-risk groups were also offered allogenic transplant as consolidation. Patients with ALL were treated with the MCP-841 protocol in the earlier part of this period and with the modified BFM-90 protocol in the later part. As for AML, patients with ALL were also offered allogenic transplants in CR-1 in those with high-risk features. Irrespective of the treatment received, the cumulative probability of OS at 5 years for the whole cohort was 40% with 5-year OS of APML, AML, and ALL being 90, 30, and 58%, respectively [Figure 2].
Hodgkin's and non-Hodgkin's lymphoma activity and outcomes
From January 1, 2010 to December 31, 2014, 3633 patients with a diagnosis of lymphoma were registered in TMH. The median age of patients with Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) was 28 years (range 3–84 years) and 52 years (range 6–90 years), respectively. The male/female ratios were 3:1 and 2.75:1, respectively. Five hundred and forty-two (15%) patients were not treated at TMH for various reasons, as illustrated in [Figure 3]. Of the remaining 3091 patients, 753 were diagnosed with HL, while 2338 were diagnosed with NHL. The median age of treated patients with HL and NHL was 48 years, while the male/female ratio was 3:1. Approximately half of all lymphomas comprised diffuse large B cell lymphoma (DLBCL) and HL as shown in [Figure 4]. The first-line chemotherapy for HL was ABVD; the same for DLBCL was CHOP + Rituximab. Rituximab + EPOCH was used for a select group of patients. Other B cell lymphomas (including follicular lymphomas) were treated with rituximab-based therapy. The cumulative probability of OS at 5 years for HL and NHL were 85 and 78%, respectively. Among the NHL, the best survival was seen in those with Burkitt's lymphoma [Figure 4].
|Figure 3: Number of registrations of all subtype of lymphomas over 5 years|
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|Figure 4: Frequency distribution of various lymphoma subtypes and OS of HL, NHL and its various subtypes|
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Multiple myeloma activity and outcomes
Between January 1, 2010 and December 31, 2014, 544 patients with multiple myeloma were registered in TMH. The male/female ratio was 2.99:1. Ninety patients did not undergo treatment in TMH for various reasons, as shown in [Figure 5]. The median age of treated patients with myeloma was 55 years, with male/female ratio of 2.9:1. The routine practice at our center is to use Bortezomib or lenalidomide-based triplet combination therapy in the front-line setting. The cumulative probability of OS at 5 years irrespective of type of treatment was 40%.
Bone marrow transplant program
The bone marrow transplant (BMT) unit of Tata Memorial Centre was started in 1983 at TMH, being the first hospital in the country to perform BMT. The transplant unit shifted from TMH to Advanced Center for Treatment, Research and Education in Cancer (ACTREC) and was commissioned on November 14, 2007. This is a six-bedded BMT unit, with each room having terminal high-efficiency particulate air (HEPA) filter. Approximately, 415 allogeneic (46%) and autologous (54%) transplants have been performed in our new center from November 14, 2007 till December 31, 2014. Number of transplants performed per year since its inception at ACTREC is shown in [Figure 6].
|Figure 6: Number of autologous and allogeneic transplants per year since November 2007|
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In order to cater to the needs of those who do not have an human leukocyte antigen-matched sibling, matched unrelated donor transplant was successfully initiated in November 2009. Similarly, unrelated cord transplant program was started in April 2010 and haploidentical transplant was successfully started in January 2013.
Outcome data of transplant in various diseases from November 2007 to December 2014
From November 14, 2007 to December 31, 2014, 415 transplants have been done in ACTREC. As shown in [Figure 7], AML and ALL comprise majority of allogeneic transplants, while HL and multiple myeloma comprise the majority of autologous transplants.
|Figure 7: Number of transplants in various diseases from November 2007- December 2014|
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The conditioning regimen for lymphoma transplants (including HL and NHL) was LACE (lomustine, cytarabine, cyclophosphamide, and etoposide) in 97% (122 of 128 lymphoma transplants). For all myeloma transplants, Melphalan was used. Of the allogenic transplants, 41 of 191 (21%) were myeloablative regimens and the remaining 140 (79%) had reduced intensity regimens. The myeloablative regimens used were either Busulfan + Cyclophosphamide or Cyclophosphamide + Total Body Irradiation. The reduced intensity regimens were all fludarabine-based regimens.
At a median follow-up of 60 months, the OS and RFS of all patients and according to type of transplant are shown in [Figure 8]. The OS and RFS of patients with AML and ALL are shown in [Figure 9]. Similarly, the OS and RFS of patients with HL and NHL, multiple myeloma, and neuroblastoma undergoing autologous transplants are shown in [Figure 10] and [Figure 11], respectively. Similarly, the OS and RFS of patients undergoing allogeneic transplants for CML and marrow failure syndromes are shown in [Figure 12]. Marrow failure syndrome comprised patients with aplastic anemia, Fanconi's anemia, and myelodysplastic syndrome.
|Figure 8: OS and RFS of all patients and according to type of transplant|
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|Figure 9: OS and RFS of patients undergoing allogeneic transplant for AML and ALL|
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|Figure 10: OS and RFS of patients undergoing autologous transplants for lymphomas|
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|Figure 11: OS and RFS of patients undergoing autologous transplants for multiple myeloma and neuroblastoma|
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|Figure 12: OS and RFS of patients undergoing allogeneic transplants for CML and marrow failure syndromes|
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Incidence of mortality and causes of death in transplant patients
There have been 167 (40%) deaths in cohort of patients that have been transplanted from November 2007 to December 2014. The overall transplant-related mortality (TRM), autologous and allogeneic TRM, and causes of death in all patients undergoing transplant are shown in [Figure 13]. Among the causes of death, 25% were attributed to TRM and 71% to relapse of the disease [Figure 13]. The TRM in autologous and allogeneic transplant were 4 and 16%, respectively.
|Figure 13: Incidence of Transplant Related Mortality in autologous and allogeneic transplants and causes of death|
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| » Discussion|| |
Given the paucity of data from India regarding the outcomes of patients with hematological malignancies treated in day to day clinical practice, the data presented here provide the outcomes of patients in a real world scenario from the largest dedicated cancer centre in India.
Among adults with acute leukemias, about two-thirds of those registered received therapy at our center. Among the treated patients with AML and ALL, long-term survival was seen in 30 and 58% patients, respectively. These data are more or less similar to those reported from other major hematology centers in India., However, we were able to treat a higher proportion of patients with AML compared to some other centers. For example, data from a large hematology center in South India showed that only about one-third of patients could be treated. The major reason for not taking treatment was financial constraints in that group of patients. We could treat a larger fraction of patients possibly because of the multitude of sources of financial support available to our center.
For HL and NHL, the scenario is slightly different. About three-fourths of patients with NHL treated at our center have a long-term survival. Registry data from various cancer centres across the entire country report an age-adjusted OS in the range of 10 to 40%. Data from one center in South India report a long-term survival in 50% of patients. These differences partly could be related to the costs of therapy and the proportion of patients completing planned therapy. For example, in the above-mentioned study from South India, only about half of the patients initiated therapy; among these less than half completed the planned therapy. The major reason for not receiving the complete treatment was again financial constraint. Not only could we treat a higher proportion of patients, but we could also complete the planned therapy in majority of patients (data not shown). Because of availability of support programs, we were able to give rituximab to >90% patients (data not shown). For patients with HL, across all stages, long-term survival probability was 85%. This is comparable to that reported from several studies from USA and Europe.,
More than 500 patients with myeloma were registered and more than 450 were treated at our center in the 5-year period from 2010 to 2014. This included newly diagnosed patients as well as pretreated patients. The 5-year survival of the overall cohort is 40%. There are no large Indian studies addressing this; however, the 5-year survival reported from Surveillance, Epidemiology and End Results (SEER) database from USA was 33%.
The institute started the stem cell transplant program in 1983 and was the first center in the country to do stem cell transplant. The transplant unit was relocated to ACTREC in Navi Mumbai in November 2007. Since then, there has been a steady increase in the number of transplants done at Tata Memorial Centre. The majority of transplants have been done for hematological disorders. Neuroblastoma and some solid tumors (like germ cell tumors and Ewing's sarcoma) constitute a minority of cases. The outcomes of transplants for various malignancies have been shown in the graphs. Over the years, there has been a gradual reduction in the TRM. This is probably because of the improvement in supportive care over the years.
To conclude, we provide data on the outcomes of a large cohort of patients with various hematological disorders treated in routine clinical practice. We expect that these will help us to identify our strengths and weaknesses; also, this will help us to find out areas where there are obstacles which we can tackle as well as where there is a scope for improvement so that we can improve the outcomes of these patients in the years to come.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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